Physiology & Behavior

Published by Elsevier
Print ISSN: 0031-9384
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Frontofrontal and frontoparietal EEG power densities (0.5-20 Hz) in waking, light and deep slow-wave sleep, transition-type sleep, and rapid-eye-movement (REM) sleep were investigated for 8 h during the light period in 16 male Wistar rats. The data indicate that as delta activity (0.5-4.5 Hz) increased from light to deep slow-wave sleep, the number of epochs per scoring epoch with high sigma activity (11-16 Hz) as well as power densities in the rest of the spectrum (5-20 Hz) including sigma frequencies also increased. This is in parallel with other rat studies but contrasts findings in humans, where EEG sigma activity is reported to decrease as sleep deepens. During the 8-h recording period, delta activity decreased whereas sigma activity increased.
 
The P3(00) event-related brain potential (ERP) was elicited with auditory and visual stimuli using an oddball task in which the subject indicated with a button-press response the occurrence of a target stimulus that occurred randomly on 20% of the trials and refrained from responding to a standard stimulus. A total of four trial blocks were collected for each stimulus modality condition. P3 amplitude from the target stimuli decreased reliably across trial blocks for both the auditory and visual stimulus condition, with no interaction obtained between stimulus modality and trial block. P3 latency was shorter for the auditory compared to visual stimulus conditions, but did not vary with trial block. No changes in amplitude or latency independent of the P3 effects were obtained for the other ERP components with trial block, although the usual modality differences were observed. The results suggest that P3 components elicited by auditory and visual stimuli both habituate for actively discriminated target stimuli. The theoretical implications are discussed in the context of previous findings.
 
Dopamine D(1) receptor blockade does not appear to be a prerequisite for antipsychotic activity since many clinically effective antipsychotics have little or no affinity for this receptor subtype. Clozapine, however, which has minimal liability for extrapyramidal symptoms, possesses affinities of similar order for D(1) and D(2) receptors. In earlier animal models used to predict antipsychotic effect, selective D(1) antagonists have shown effects similar to standard antipsychotics with preferential D(2) or mixed D(1)/D(2) antagonism. We investigated the effects of haloperidol (0.1 mg/kg) and two selective D(1) antagonists, NNC 01-0112 (0.05, 0.1 and 0.2 mg/kg) and SCH 39166 (0.02, 0.2 and 2.0 mg/kg), on latent inhibition (LI) in rats. LI is a behavioural paradigm in which repeated nonreinforced preexposure to a stimulus retards subsequent associations to that stimulus. Disrupted LI has been suggested as a model for the attentional deficits in schizophrenia. Using preexposure to a flashing light stimulus, which subsequently served as a conditioned stimulus for suppression of water licking, we demonstrated a clear LI effect with haloperidol but with neither of the two D(1) antagonists. Since selective D(1) antagonists are not clinically effective, these results add further credibility for the relevance of LI as an animal model of psychosis.
 
N-0437 is a potent and highly selective dopamine D-2 receptor agonist, which has been used in the present series of experiments to investigate its potential anorectic properties. In doses of 0.3-3.0 mg/kg (IP), N-0437 significantly reduced consumption of a sweetened palatable mash in nondeprived mice (minimal effective dose, 0.3 mg/kg) and rats (minimal effective dose, 0.56 mg/kg). Reduction in food intake were also produced in rats by the less potent, but selective, D-2 agonist RU 24213 (effective at 10.0 mg/kg), and by d-amphetamine (1.0 and 3.0 mg/kg). The anorectic effect of N-0437 (1.0 mg/kg) was completely antagonized by the selective D-2 antagonist, YM-09151-2 (0.01 mg/kg). Over a series of 10 injections, N-0437 (1.0 mg/kg) maintained its effect to reduce palatable food intake. In food-deprived rats, N-0437 (0.3-3.0 mg/kg, IP) also reduced consumption of standard laboratory food, and dose-dependently reduced operant responding for food under a FR8 schedule of reinforcement. The results of the experiments are discussed in terms of a possible direct effect to reduce feeding responses resulting from stimulation of postsynaptic dopamine D-2 receptors.
 
Yawning and stretching responses were elicited in rats by a small dose (0.3 mg/kg) of the highly selective dopamine D2 agonist, N-0437. The responses were blocked by the highly selective dopamine autoreceptor antagonist, (+)-UH 232 (3.0 mg/kg), but not by raclopride at a dose which selectively blocks postsynaptic D2 receptors. The results strongly confirm the view that yawning and stretching are behavioral responses elicited by stimulation of presynaptic D2 receptors.
 
The effect of ATD on olfactory investigation in intact and in castrated, testosterone-treated male hamsters was studied using subcutaneous silastic implants. In intact males, there was a dose-dependent action of ATD in reducing sniffing towards novel females and in eliminating the discrimination between females after pre-exposure to vaginal odour. Both sniffing and olfactory discrimination reappeared after removal of ATD implants. Neither the weight nor the general behavioural activity of treated males was affected, indicating a specific behavioural affect. Testosterone (T) maintained olfactory behaviour in castrated males. Untreated castrates and castrates with ATD + T implants showed reduced sniffing and showed no discrimination between females after exposure to female odour. We conclude that conversion of T to oestrogen plays an essential role in the control of male olfactory behaviour.
 
1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.
 
Pups from gestating rats exposed to hypergravity (1.8 G) or to normal gravity at the perinatal period were evaluated for motor activity, exploration and social interactions during juvenile and adult stages. By comparison to controls, the hypergravity group had shorter latencies before choosing a maze arm in a T-maze and a lower number of exploratory pokes in a hole board. During dyadic encounters, the hypergravity group had a lower number of self-grooming episodes and shorter latencies before crossing under the opposing rat. In contrast, no intergroup differences were observed during exploration of an elevated plus-maze and a light-dark box. These results indicate that exposure to 1.8 G during development appears to decrease exploratory tendencies in the hole board and fear-related responses in T-maze and social interaction tests.
 
The effects on anxiety and risk assessment of exposure to a cat were tested in hooded rats. Anxiety and risk assessment were measured in an elevated plus maze and hole board in a room different from the cat-exposure room. Behavior was tested either 1, 2, 7, 14, or 21 days after cat exposure in different groups of rats. A single exposure to a cat increased anxiety over controls in the plus maze from 1 to 21 days after exposure to a cat. The effects on anxiety were independent of activity or exploratory tendency. Severity of anxiety produced was predicted by the approach, but not the attack, behavior of the cat. Analogous correlations between traumatic stimuli and anxiety are seen in humans suffering from posttraumatic stress disorder (PTSD). Risk assessment in the plus maze was reduced over the same period in rats exposed to cats. Risk assessment was weakly correlated with anxiety. The findings are discussed with respect to the potential of this phenomenon as a model of generalized anxiety disorder found in PTSD.
 
This article is based on proceedings of a symposium presented at the 2002 meeting of the Society for the Study of Ingestive Behavior and provides a brief overview of recent research suggesting a role for neuropeptide Y (NPY) in the modulation of ethanol drinking. The discussion focuses mainly on recent studies with genetic animal models including mutant mice lacking specific NPY receptor and selectively bred rodents, namely the Indiana alcohol-preferring (P) and alcohol-nonpreferring (NP) rats and the Indiana high alcohol drinking (HAD) and low alcohol drinking (LAD) rats. It is concluded that abnormal or low central NPY activity can promote high alcohol drinking and that NPY modulates alcohol consumption via the NPY Y1 and Y2 receptors.
 
Environmental conditions promote weight gain in children and adults, with early nutritional states and the availability of energy condensed/high-fat palatable diets appearing to facilitate the development of obesity. Little is known about the extent to which prenatal and postnatal dietary manipulations alter the response of the adult offspring to high-fat, highly palatable diets. Here we exposed rat dams to highly palatable diet (supplemental diet, SD), rich in fat and sugars, during pregnancy and lactation, and assessed the potential interactions with the effects of a similar diet offered post-weaning on a range of physiological and behavioral parameters in the adult male offspring. Post-weaning exposure to SD increased body weight, body fat, and plasma leptin levels, as well as the plasma glucose response to glucose challenge, compared to chow-fed rats. Combining perinatal SD with post-weaning exposure (SD/SD group) elevated fasting plasma glucose levels, and induced leptin resistance in the adult rats. The same treatment also resulted in sensitized locomotor response to an acute injection of amphetamine. The glucocorticoid response to stress was not affected by the dietary treatments. We conclude that exposure of mother and young to a highly palatable diet with high-fat and high sugar content during the critical perinatal period, increases the risk of developing an obesity-like condition in rats exposed to the same palatable diet post-weaning, and this effect may be accompanied by adaptations in the reward-related mesostriatal dopaminergic system.
 
Stress-related psychiatric disorders, such as depression and anxiety, affect a disproportionate number of women. We previously demonstrated that the major brain norepinephrine (NE)-containing nucleus, locus coeruleus (LC) is more sensitive to stressors and to the stress-related neuropeptide, corticotropin-releasing factor (CRF) in female compared to male rats. Because the LC-NE system is a stress-responsive system that is thought to be dysregulated in affective disorders, sex differences in LC structure or function could play a role in female vulnerability to these diseases. The present study used different approaches to compare LC dendritic characteristics between male and female rats. Immunofluorescence labeling of tyrosine hydroxylase, the norepinephrine synthetic enzyme, revealed that LC dendrites of female rats extend further into the peri-LC region, covering a significantly greater area than those of males. Optical density measurements of dendrites in the peri-LC revealed increased dendritic density in females compared to their male counterparts. Additionally, immunoreactivity for synaptophysin, a synaptic vesicle protein, was significantly greater in the LC in female rats, suggesting an increased number of synaptic contacts onto LC processes. Individual LC neurons were juxtacellularly labeled with neurobiotin in vivo for morphological analysis. LC dendritic trees of females were longer and had more branch points and ends. Consistent with this, Sholl analysis determined that, compared to males, LC dendrites of females had a more complex pattern of branching. The greater dendritic extension and complexity seen in females predicts a higher probability of communication with diverse afferents that terminate in the peri-LC. This may be a structural basis for heightened arousal in females, an effect which may, in part, account for the sex bias in incidence of stress-related psychiatric disorders.
 
Research has focused on understanding how overeating can affect brain reward mechanisms and subsequent behaviors, both preclinically and in clinical research settings. This work is partly driven by the need to uncover the etiology and possible treatments for the ongoing obesity epidemic. However, overeating, or non-homeostatic feeding behavior, can occur independent of obesity. Isolating the variable of overeating from the consequence of increased body weight is of great utility, as it is well known that increased body weight or obesity can impart its own deleterious effects on physiology, neural processes, and behavior. In this review, we present data from three selected animal models of normal-weight non-homeostatic feeding behavior that have been significantly influenced by Bart Hoebel's 40+-yr career studying motivation, feeding, reinforcement, and the neural mechanisms that participate in the regulation of these processes. First, a model of sugar bingeing is described (Avena/Hoebel), in which animals with repeated, intermittent access to a sugar solution develop behaviors and brain changes that are similar to the effects of some drugs of abuse, serving as the first animal model of food addiction. Second, another model is described (Boggiano) in which a history of dieting and stress can perpetuate further binge eating of palatable and non-palatable food. In addition, a model (Boggiano) is described that allows animals to be classified as having a binge-prone vs. binge-resistant behavioral profile. Lastly, a limited access model is described (Corwin) in which non-food deprived rats with sporadic limited access to a high-fat food develop binge-type behaviors. These models are considered within the context of their effects on brain reward systems, including dopamine, the opioids, cholinergic systems, serotonin, and GABA. Collectively, the data derived from the use of these models clearly show that behavioral and neuronal consequences of bingeing on a palatable food, even when at a normal body weight, are different from those that result from simply consuming the palatable food in a non-binge manner. These findings may be important in understanding how overeating can influence behavior and brain chemistry.
 
The amygdala is involved in the emotional responses to fear including anxiety and heightened pain reporting. In a rodent model, bilateral activation of the central amygdala (CeA) with corticosterone (CORT) produces anxiety-like behavior, somatic allodynia and visceral hypersensitivity. Although hemisphere-specific processing differences between the left and right amygdala have been reported, it remains unclear whether the right or left CeA is involved in the production of anxiety-like behavior, and abnormal somatic and visceral perception. The goal of the present study was to investigate the hypothesis that lateralized corticoid-mediated mechanisms in the CeA produce anxiety as well as abnormal pain perception. Anesthetized rats received stereotaxic implants of cholesterol (Chol; 30 μg) or CORT (30 μg) micropellets onto the left, right or both dorsal margins of the CeA. Following implantation (5-7 days), anxiety-like behavior was assessed on the elevated plus-maze (EPM), somatic allodynia was measured using Von Frey filaments, and visceral sensitivity was quantified as a visceromotor response (VMR) to colorectal distention (CRD) at 0-60 mmHg. Unilateral implants of CORT onto either the left or right CeA produced anxiety-like behavior and somatic allodynia. However, our data illustrated that the bilateral placement of CORT onto the CeA was required to increase visceral sensitivity. These results provide evidence that there is no hemispheric lateralization of the CeA involved in corticoid-mediated anxiety-like behavior and heightened pain reporting.
 
Significant sex differences have been demonstrated in clinical and preclinical studies of cocaine addiction, with some of the most consistent differences noted in regard to the role of stress and craving. The current study examined stress-induced reinstatement of cocaine seeking in male and female rats in an animal model of relapse using corticotropin-releasing factor (CRF) administration. Both male and female rats demonstrated increased cocaine seeking in response to CRF. CRF-induced reinstatement was highly variable across both male and female rats, and further analysis revealed a subpopulation that was particularly sensitive to CRF (high responders). Female high responders displayed significantly increased responding to CRF compared to males. Individual differences in stress responsivity could thus contribute to the likelihood of relapse, with females showing greater heterogeneity to stress-induced relapse.
 
The adrenocortical and gonadal responses of 14 male monkeys were evaluated during four experimental conditions in order to evaluate the influence of social interactions on endocrine responsiveness. Plasma hormone levels were determined during the establishment of social relations, after 60-min exposures to a novel environment, after 60-min exposures to a snake, and 60 min after ACTH administration. Both adrenal and gonadal secretion changed significantly during the first day after social relations were established, although only dominant males showed increases in testosterone, whereas cortisol levels rose in all subjects. Increases in cortisol, but not testosterone, were also observed following exposure to novelty or a snake. The presence of a social partner reduced signs of behavioral disturbance during these test conditions, although the adrenal responses were equivalent or greater than when tested alone. This finding qualifies earlier research which indicated that social support was beneficial for reducing stress when squirrel monkeys were tested in larger groups in their home environment.
 
The leopard gecko has temperature-dependent sex determination (TSD); females are predominantly produced when incubated at 26 degrees C (100%), 30 degrees C (70%), and 34 degrees C (95%), whereas males are predominantly produced at 32.5 degrees C (75%). Exogenous estradiol can override the effect of temperature on sex determination. To compare temperature-determined females with hormone-determined females, eggs from the male-biased temperature were treated with estradiol benzoate during incubation. As adults, animals from a male-biased incubation temperature were more likely to exhibit aggression than animals from female-biased incubation temperatures. Furthermore, females from a male-biased incubation temperature tended to be less attractive than females from female-biased temperatures. Hormone-determined females were both attractive and aggressive. This suggests that incubation temperature is an important development determinant of adult aggressiveness and attractiveness. The 26 degrees C animals ovariectomized on the day of hatch exhibited more frequent aggression and were unreceptive to males, indicating that postnatal ovarian hormones also play a role in adult sociosexual behaviors. The parallel between incubation temperature and intrauterine position in laboratory mammals is discussed.
 
We compared the effects of CGS 10686B (a new drug that blocks serotonin reuptake), on nutrient selection and total food consumption with those of two other serotoninergic drugs, dl-fenfluramine and fluoxetine. The animals were given simultaneous free access to two isocaloric 40%-carbohydrate diets in separate food pans; one of these diets (5% protein) was shown to enhance brain serotonin synthesis by raising brain tryptophan levels; the other (45% protein) did not. CGS 10686B (4-7.5 mg/kg) markedly decreased (60-70%) consumption of the 5% protein diet, with a smaller effect (20-30%) on consumption of the 45% protein diet. Hence, it increased the ratio of protein to carbohydrate in the total food consumed. Higher doses (12.5-15 mg/kg) were no longer nutritionally-specific. Fluoxetine, which also blocks serotonin reuptake, and dl-fenfluramine, which both releases serotonin and suppresses its reuptake, had similar effects on nutrient intake; dl-fenfluramine was most potent and fluoxetine least. None of the drugs selectively affected carbohydrate or protein intake if the composition of the test diets provided was such that neither diet, eaten alone, would increase brain serotonin. These observations affirm that drugs which enhance serotoninergic neurotransmission selectively suppress the intake of high-carbohydrate, low-protein meals which increase brain serotonin synthesis.
 
Any odor-guided behavior might require generalization and/or discrimination over a wide range of odorant intensities. Proboscis extension conditioning (PEC) and electroantennogram (EAG) assays were used to investigate stimulus-intensity dynamics during olfactory processing in the honey bee. Experiments that tested generalization involved conditioning to one odorant concentration and either testing with a different odorant or with different concentrations of the same odorant. At low training concentrations, responses to either a novel odorant or to higher concentrations of the same odorant resulted in strong generalization. At higher training concentrations, significantly less generalization was observed to a novel odorant or to lower concentrations of the same odor. EAG analyses indicate that asymmetric generalization could arise due to long-term adaptation of peripheral receptor neurons. Discrimination experiments showed that relatively higher odorant concentrations associated with an appetitive reinforcer could usually be discriminated from a lower concentration that was associated with punishment, but not vice versa. Although sensory modulation in peripheral (sensory) processes might be sufficient to account for discrimination of a high from a low concentration, discrimination of low from high concentrations point to the involvement of central processes.
 
A combination of cannabis with even a small amount of ethanol can alter the brain function, more than either drug alone. To investigate the interacting effects of the co-administration of a low dose of ethanol and a cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA) on the conditioned place preference (CPP) test in male Wistar rats, ACPA was injected into the ventral tegmental area (VTA), basolateral amygdala (BLA) or ventral hippocampus (VH) in combination with ethanol during the conditioning or testing phase. Using a 3-day schedule of conditioning, low doses of ethanol (0.25, 0.5 and 1g/kg, i.p.) did not induce CPP or conditioned place aversion (CPA). In the second experiment, bilateral intra-VTA injection of the cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA; 0.5 and 1ng/rat) alone or with ethanol (0.5g/kg) induced a significant CPA. Bilateral intra-BLA injection of ACPA induced significant CPP, while co-administration of the same doses of ACPA with ethanol (0.5g/kg) induced CPA. Bilateral intra-VH injection of ACPA by itself produced both CPP and CPA in a dose-dependent manner. Co-administration of an ineffective dose of ACPA (9ng/rat, intra-VH) with ethanol also induced significant CPA. In the animals that had received ethanol during the conditioning phase, intra-VTA or -VH injection of ACPA, 5min before the testing phase, produced CPP while intra-BLA injection of the agonist produced CPA. None of the treatments, except intra-VH injection of ACPA, had an effect on locomotor activity. In conclusion, there may be a functional interaction between endocannabinoid system and ethanol in mediating reward or aversion.
 
Progesterone treatments have been shown to increase nesting levels of isolated female mice. Here we compared the effect of exogenous progesterone on the nesting behavior of C57BL/10Sn female Mus domesticus housed individually to nesting levels of the same mice housed in pairs. Progesterone increased nesting by isolated females but had no significant effect on the nesting scores of the same mice when they were grouped into pairs. The effect of exogenous progesterone on nesting levels in C57BL/10Sn females appears to depend on social circumstances.
 
Ten Hooded Lister rats were divided from weaning into two groups of five. One group was fed exclusively on a liquid diet in the home cage (Complan-fed subjects), the other group was given normal laboratory chow (Chow-fed subjects). At approximately 60 days of age both groups were reduced to 80% of their ad lib body-weight and given pairings of a retractable lever (conditioned stimulus, CS) and response-independent food (unconditioned stimulus, UCS). In the first experimental condition a liquid UCS was used (condensed milk solution) and in later conditions this was substituted with a solid UCS (45 mg food pellet). Analysis of CS-directed behavior in the two groups suggested that (1) only very early in autoshaping training did feeding experience in the home cage influence the topography of signal-directed behavior, and subsequently (2) both Complan-fed and chow-fed subjects bit rather than licked the CS paired with a solid UCS and licked rather than bit the CS when it was paired with a liquid UCS. These results suggest that, in the long-term, the topography of signal-centered behavior in rats is more likely to be influenced by the nature of the reinforcer signalled by the CS than by the subject's feeding experiences during early development.
 
The family of the endocannabinoid system comprises endogenous lipids (such as anandamide, [ANA]), receptors (CB(1)/CB(2) cannabinoid receptors), metabolic enzymes (fatty acid amide hydrolase [FAAH]) and the putative membrane transporter (anandamide membrane transporter [AMT]). Although the role of ANA, FAAH or the CB(1) cannabinoid receptor in sleep modulation has been reported, the effects of the inhibition of AMT on sleep remain unclear. In the present study, we show that microdialysis perfusion in rats of AMT inhibitors, (9Z)-N-[1-((R)-4-hydroxbenzyl)-2-hydroxyethyl]-9-octadecenamide (OMDM-2) or N-​(4-​hydroxy-​2-​methylphenyl)-​5Z,​8Z,​11Z,​14Z-​eicosatetraenamide (VDM-11; 10, 20 or 30μM; each compound) delivered into the paraventricular thalamic nucleus (PVA) increased sleep and decreased waking. In addition, the infusion of compounds reduced the extracellular levels of dopamine collected from nucleus accumbens. Taken together, these findings illustrate a critical role of AMT in sleep modulation.
 
PN200-110 is a recently introduced 1,4-dihydropyridine which has been demonstrated to be a potent calcium channel blocker. 3HPN has been shown to bind in a specific saturable manner to P2 fractions obtained from brain homogenates from male Sprague-Dawley rats. 3HPN binding was found to be temperature-dependent. Specific 3HPN binding was maximal at 25 degrees C; binding decreased at 2 degrees C and 37 degrees C. The KD calculated from Scatchard analysis was 0.0943 +/- 0.0038 nM while the Bmax was found to be 109.1 +/- 2.3 fmol/mg protein. A concentration dependent inhibition of 3HPN binding by various cations was determined and found to be as follows: ZN2+ greater than La3+ greater than Rh3+, Al3+ greater than Co2+, Ni2+, Mn2+ greater than Ca2+, Mg2+ greater than Ba2+ greater than Sr2+. These results provide evidence for the existence of central high affinity dihydropyridine receptor sites in rat brain.
 
Using microdialysis in freely moving rats, we have been able to observe changes in monoamines from the ventromedial and paraventricular hypothalamic nuclei before, during, and after spontaneous feeding. Because the genetically obese Zucker rat shows abnormalities related both to feeding and monoamines, it was of interest to investigate possible particularities in the monoaminergic variations around spontaneous feeding. The profile of changes in Zucker rats was grossly similar to that of Wistar rats: increases in 5-hydroxy-tryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA), and dopamine (DA), and decrease in dihydroxyphenylacetic acid (DOPAC). However, the release in monoamines (5-HT and DA) was more dramatic and longer-lasting than in Wistar rats, while the changes in the metabolites were proportionnally less pronounced. This suggests that high concentrations of these feeding-related amines are released and remain in the synaptic cleft of the obese rat, possibly because they are required in larger amounts to bring about satiety. The hyperphagia of the obese Zucker rat may therefore be the result of a resistance to these prandially released satiety-promoting neurosubstances.
 
An improved guinea pig headholder, designed to provide long-term and reliable head fixation, was developed. It consists of a mouthpiece, nose clamp, and pivoting backing block. The advantages of this headholder are i) the correspondence of the mouthpiece to the anatomical peculiarities of the guinea pig skull, ii) automatic positioning for snout fixation, and iii) application of the load to sites of the skull that are strong, the latter of which prevents tissue damage. The headholder fits guinea pigs weighing 400-750 g and permits free access to all brain regions.
 
Numerous theoretical as well as pharmacological arguments lead to the assumption that anxiety and memory are two closely linked concepts. Nevertheless, the study of this relationship is full of complexities because neither memory nor anxiety are unitary phenomena. Indeed, the term memory covers a large number of concepts, and anxiety has been divided in two main classes, "state" and "trait" anxiety. Recently the neophobic responses exhibited by Balb/c mice confronted to the free exploratory paradigm have been proposed as a "trait anxiety" model while response exhibited in the light/dark choice procedure as a "state anxiety" one. The aim of this study was to further clarify the link between these two anxiety types and memory of emotional events assessed in the passive avoidance test. The relationship between the variables measured in these three tests were assessed by a principal component analysis that confirmed that the behavior recorded in the two anxiety tests does not reflect the same psychological state, and showed that emotional memory is linked to "state" but not "trait" anxiety.
 
These experiments examined the role of gonadal hormones at both the organizational and activational time periods on sex differences in plus-maze behavior. In the first experiment, adult female Long-Evans rats were found to spend more time on the open arms of the plus maze than adult males, indicating less anxious behavior. In the second experiment, male and female subjects received a neonatal treatment (chemical castration with flutamide or tamoxifen, vehicle injection, or no injection) and a prepubertal treatment (gonadectomy, sham surgery, or no surgery). Adult females receiving either neonatal tamoxifen or prepubertal ovariectomy spent less time on the open arms than control females, but females who received both treatments were the most defeminized subjects. Males were not affected by the absence of gonadal hormones at either time period. These experiment indicate that female gonadal hormones play an important role both organizationally and activationally in plus-maze behavior. The role of the GABA receptor complex in mediating this effect is discussed. Knowledge of sex differences in plus-maze behavior may help to make this maze a more useful tool in investigating anxiety behavior in rats.
 
α7 Nicotinic acetylcholine receptors (α7nAchRs) modulate immune activation by suppressing production of pro-inflammatory cytokines in peripheral immune cells. α7nAchRs also modulate inhibitory output in the hippocampus, which provides input to key circuits of the HPA axis. Therefore, the α7 nicotinic acetylcholine receptor gene (CHRNA7) may be associated with cortisol stress response. Polymorphisms in the CHRNA7 promoter decrease its expression and may dampen the cholinergic response, leading to an increase in inflammation. Increased inflammation may change the intrauterine environment, altering neuroendocrine development in the offspring. Maternal CHRNA7 genotype could affect an offspring's HPA regulation via reprogramming in utero. Patients with allergic disorders have a differential cortisol response to stress. This study utilized samples collected from a cohort of 198 adolescents in a previous study of atopic disorders, who demonstrated a disturbance in HPA response associated with atopy. Salivary cortisol samples collected from the adolescents after a series of laboratory procedures and DNA samples collected from the adolescents and their parents were used for further analysis. DNA samples were genotyped for allelic variation in the CHRNA7 promoter. Genetic association analyses with the cortisol levels were performed in the adolescents. Maternal genotype influences were investigated for the CHRNA7 gene. We also included maternal and child atopy diagnosis as covariates in determining cortisol levels and tested for association of CHRNA7 to atopy. Polymorphisms in the CHRNA7 promoter were associated with lower cortisol levels after a small laboratory stress. Our findings also show that although the child's CHRNA7 genotype affects stress response, the maternal genotype has a stronger influence on cortisol release after stress in male offspring. These effects were independent of atopy status.
 
The long-term consequences of a single social defeat on open field behaviour in rats were studied, with special emphasis on the time course of stress-induced changes. Animals were subjected to social defeat by placing them into the territory of an aggressive male conspecific for 1 h. After the defeat session experimental animals were returned to their home cage and their own room, receiving no further cues from the resident. Other animals serving as controls were placed in a clean and empty cage for 1 h. Five-minute open field tests were performed on days 1, 2, 7, 14, and 28 after defeat, with independent groups of rats. Locomotion of the animals was recorded and analyzed with an automated video system. Social defeat resulted in a strong subsequent reduction in open field activity, which lasted till at least 7 days after the conflict. Differences in total travelled distance were no longer significant 2 weeks after the conflict. The latency for moving to the outer ring of the open field arena after the start of the test was still significantly longer 4 weeks after defeat. The stress-induced reduction in open field locomotion could be reversed by 12-h sleep deprivation during the resting phase, an intervention known to have antidepressant effects in humans. Possible relevance of the present findings with respect to human affective disorders is discussed.
 
To examine mechanisms responsible for sex differences in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to stress, we studied the role of androgens in the regulation of the adrenocorticotropin (ACTH) and corticosterone (CORT) responses to foot shock and novelty stressors in gonadectomized (GDX) or intact male F344 rats. Foot shock or exposure to a novel open field increased plasma ACTH and CORT, which was significantly greater in GDX vs. intacts. Testosterone (T) or dihydrotestosterone propionate (DHT) treatment of GDX animals returned poststress levels of ACTH and CORT to intact levels. Estrogen treatment of GDX males further increased poststress CORT secretion above GDX levels. There was no difference in the ACTH response of anterior pituitaries from intact, GDX, and GDX+DHT animals to CRF using an in vitro perifusion system. There were no differences in beta max or binding affinity of type I or II CORT receptors in the hypothalamus or hippocampus of intact, GDX, or GDX+DHT groups. These data demonstrate an effect of GDX on hormonal indices of stress. The increased response in GDX rats appears to be due to the release from androgen receptor mediated inhibition of the HPA axis. This inhibition by androgen is not due to changes in anterior pituitary sensitivity to CRH, nor to changes in type I or type II corticosteroid receptor concentrations.
 
Growing evidence indicates that there is a correlation between depression and inflammation. Administration of anti-tumour necrosis factor (TNF) agents for treatment of chronic inflammatory diseases, such as psoriasis, was associated with decreased depressive symptoms and increased quality of life in some clinical studies. The aim of the present study was to investigate the effects of chronic etanercept, a TNF-α inhibitor, on anxiety- and depression-like neurobehaviors in rats. Male rats were treated for 8 weeks with either saline or etanercept (0.8 mg/kg/week, subcutaneously). The anxiety levels of rats were evaluated using the elevated plus maze, a classical rodent model of anxiety and depression was measured using the force swimming test, a behavioral despair task. The anxiety-like neurobehaviors of the animals were found significantly decreased after the etanercept treatment. Etanercept significantly decreased immobility time in rat model of despair test, seemed to have an antidepressive effect in rats. Compared to saline treatment, long-term etanercept treatment had no effect on the total number and pattern of locomotor activities. Findings of the study supported the hypothesis that TNF-α has a role in the modulation of emotional processes and its inhibition may represent a novel strategy for the treatment of affective disorders.
 
Mice acquire strong preferences for flavors paired with intragastric (IG) fat infusions. This IG fat conditioning is attenuated in double knockout (DoKO) mice missing GPR40 and GPR120 fatty acid receptors. Here we determined if GPR40/120 DoKO mice are also impaired in IG fat self-administration in an operant lick task. In daily 1-h sessions the mice were trained with a sipper spout that contained dry food pellets; licks on the spout triggered infusions of IG fat (Intralipid). The training sessions were followed by test sessions with an empty spout. GPR40/120 DoKO mice self-infused more 20% fat than wild type (WT) C57BL/6 mice in training with a food-baited spout (2.4 vs. 2.0 kcal/h) but self-infused less 20% fat than WT mice in empty spout tests (1.2 vs. 1.7 kcal/h). The DoKO mice also self-infused less 5% fat than WT mice (0.6 vs. 1.3 kcal/h) although both groups emitted more licks for 5% fat than 20% fat. The DoKO and WT mice did not differ, however, in their self-infusion of 12.5% glucose (1.5 vs. 1.6 kcal/h), which is isocaloric to 5% fat. A second 5% IL test showed that the DoKO mice reverted to a reduced self-infusion compared to WT mice. When the infusion was shifted to water, WT mice reduced licking in the first extinction session, whereas DoKO mice were less sensitive to the absence of infused fat. Our results indicate that post-oral GPR40/120 signaling is not required to process IG fat infusions in food-baited spout training sessions but contributes to post-oral fat reinforcement in empty spout tests and flavor conditioning tests. Copyright © 2015. Published by Elsevier Inc.
 
Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.
 
Peripherally administered beta3-adrenergic receptor (beta3-AR) agonists stimulate lipolysis and inhibit food intake. To test the hypothesis that this inhibition of feeding is due to a substrate-driven increase in hepatic fatty acid oxidation (FAO), we assessed the ability of the FAO inhibitor mercaptoacetate (MA) to reverse the feeding-inhibitory effect of the beta3-AR agonist CGP 12177A (CGP). Adult male Sprague-Dawley rats received intraperitoneal injections of 1 mg/kg CGP, of 45.6 mg/kg MA, or of both drugs, and the effects on food intake, plasma free fatty acids (FFA), and plasma beta-hydroxybutyrate (BHB), an indicator for hepatic FAO, were assessed. Control rats received saline injections. CGP significantly reduced food intake after 0.5 and 6 h and increased plasma FFA and BHB at 0.5 h, suggesting increased lipolysis and hepatic FAO. MA completely reversed the increase in plasma BHB and thus appeared to effectively abolish CGP's effect on hepatic FAO, but MA failed to affect CGP's feeding-inhibitory action. These findings do not support the hypothesis that the beta3-AR agonist CGP inhibits feeding by enhancing hepatic FAO or ketogenesis. Although the beta3-AR agonist CGP reduced saccharin intake in a one-bottle condition taste aversion test, it seems unlikely that the hypophagic effect of CGP is elicited by malaise.
 
To describe and evaluate behavioral models of binge-type eating. Studies were identified using Medline and hand searches of bibliographies of identified articles. Isomorphic studies were selected that were judged to have some measure of construct validity. Face and construct validity were assessed, as well as simplicity and cost of use. Several different models of binge-type eating exist, each with different strengths of validity and use. These include models using sham feeding, restriction/refeeding cycles and/or stress, limited access (LA) to optional foods, and eating induced by operant schedules of behavior. We concur with Harry Harlow, who was quoted by Gerry Smith as saying: "You'd be crazy to use animal models, but you'd also be crazy not to use them."
 
Administration of RDS-127 (3.0 mg/kg) induced seminal emission within three minutes of IP injection and suppressed the display of penile reflexes in intact and spinally transected rats. In Experiment 1, RDS-127 was administered to intact, sexually experienced rats in a protocol previously demonstrated to selectively lower the ejaculatory threshold of copulating animals. The incidence of seminal emission was significantly elevated by RDS-127 but penile reflexes were present in only 8% of the drug-treated rats, compared to 59% of controls. In Experiment 2, seminal emission was induced 2.3 +/- 0.4 (S.E.) minutes from injection of RDS-127. Animals which responded to RDS-127 with multiple emissions had significantly lower ejaculation latencies during copulatory tests conducted prior to drug treatment than animals which had no or only single seminal emissions following RDS-127 injection. Spontaneous seminal emission in the 3 day period initiated 2 hours after RDS-127 injection was unaffected by the drug. Spontaneously produced plugs were approximately twice the weight of those induced by RDS-127. In Experiment 3, seminal emission was induced in spinally transected rats 1.7 +/- 0.4 minutes following RDS-127 administration, whereas drug treatment attenuated the enhancement of penile reflexes observed following midthoracic spinal transection. These experiments suggest that a spinally-mediated dopaminergic mechanism is capable of stimulating seminal emission acutely in the rat and inhibiting the display of penile reflexes by the supine animal.
 
Selective changes in the mating pattern occurred 30 minutes following administration of RDS-127 (3.0 mg/kg, IP) to sexually experienced adult male rats. Marked decreases in intromission frequency and ejaculation latency were observed. These data indicate a potent effect upon conummatory mechanisms underlying copulatory behavior. The lack of effect upon arousal state was further demonstrated utilizing a "mounting test" (in which the penis is anesthetized by topical application of tetracaine hydrochloride). No difference in mounting behavior was seen. Seminal plugs were noted in a large percentage of treated animals at the time of anesthetic application. Additionally, a six-fold decrease in plasma prolactin and a lesser decrement in plasma luteinizing hormone were evident. Finally, in sexually experienced castrate animals, RDS-127 induced mounting in two thirds and intromissive and ejaculatory patterns in one third of the treated animals, 35 days postcastration. These effects were greatly attenuated by 56 days postcastration. The selective alteration of consummatory mechanisms, with little or no effect upon arousal status, suggests a neurochemical separation of these two components in the intact male rat.
 
Metergoline, a serotonin-receptor antagonist, when administered in either an ascorbic acid or ethanol containing vehicle was without effect on male rat copulatory behavior (3 mg/kg, 90 minutes pretest). When initially dissolved in several drops of acetic acid, however, the same dose of metergoline dramatically suppressed male rat sexual behavior. Thus, one-half of the treated rats failed to intromit and ejaculate, and those displaying the behaviors exhibited elongated intercopulatory and postejaculatory intervals. The administration of the putative dopamine-receptor agonist RDS-127 (2-N,N-di-n-propylamino-4,7-dimethoxyindane; 3 mg/kg, six minutes pretest) induced seminal emission ex copula and drastically reduced intromission frequency and ejaculation latency in copula, as well as effecting lesser reductions in the intercopulatory and postejaculatory intervals in two sequential copulatory series. RDS-127-induced seminal emission was effectively antagonized by pretreatment with the dopamine-receptor antagonist pimozide (250 micrograms/kg, two hours pretest), but not by pretreatment with metergoline. In contrast to seminal emission ex copula, pimozide pretreatment failed to antagonize the RDS-127 facilitation of ejaculatory behavior in copula. Metergoline pretreatment also failed to antagonize the RDS-127-induced facilitation of ejaculatory behavior in copula. However, RDS-127 prevented the suppressive effects of metergoline treatment, suggesting that RDS-127 has some agonistic action at serotonergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 
C57BL/6J (B6) mice display stronger preference and acceptance for various sweeteners than do 129 mice (129P3/J, 129X1/SvJ). The present experiment compared the preference of these strains for fat flavor as well as sweet taste using 24-h two-bottle preference tests. Fat flavor preference was evaluated using non-nutritive (olestra) and nutritive (Intralipid) oil emulsions. In initial oil vs. water tests olestra preference and intake were greater in B6 mice than 129 mice. Similar strain differences were obtained with low (0.313%-5%) but not high (10%-20%) Intralipid concentrations. When retested with Intralipid the B6 and 129 mice showed strong (>90%) preferences for the nutritive oil although B6 mice still consumed more oil at low concentrations. A second olestra test revealed increased oil preference and acceptance in B6 and 129X1/SvJ mice while 129P3/J mice still did not prefer olestra to water. Sweetener tests revealed stronger saccharin and sucrose preferences in B6 mice than in 129 mice. These strain differences in sweetener preference disappeared when the mice were retested with sucrose and saccharin. However, B6 mice continued to consume more saccharin and sucrose (at low concentrations) than did 129 mice. The profile of strain differences for non-nutritive and nutritive oils was similar to those observed for non-nutritive and nutritive sweeteners. The differential sweetener preferences of B6 and 129 mice is explained by differences in their sweet taste receptors but why the strains also differ in their initial fat flavor preference is not clear. The experientially-induced increases in oil and sweetener preferences displayed by the mice are attributed to the post-oral actions of Intralipid and sucrose. These findings along with intragastric infusion data suggest that B6 and 129 mice differ in their oral but not their post-oral response to fat and sugar.
 
Knockout mice are typically generated on a mixed genetic background and, as such, detailed behavioural characterisation of these background strains is essential to the valid interpretation of mutant phenotypes. In this context, recent research has revealed significant differences in anxiety-like behaviour among the most commonly used background strains (C57BL/6J and various 129 substrains), leading to the possibility that at least certain mutant phenotypes may not after all be due to the targeted mutation. However, these findings derive largely from behavioural test batteries in which there may well be an experiential confound, while the widely reported hypolocomotor profile of most 129 substrains may compromise the principal indices of anxiety-like behaviour. In the present study, we have compared the behavioural profiles of three commonly used background strains (C57BL/6JOlaHsd, 129/SvEv and 129S2/SvHsd) in two of the most popular animal models of anxiety-the elevated plus-maze (EPM) and light/dark exploration (LDE) tests. Naive animals were used for each procedure, ethological scoring methods were employed throughout, and the inbred phenotypes were also compared with that of an outbred strain (Swiss-Webster) widely employed in test validation and behavioural pharmacology. Our results show that, despite their hypolocomotor profile, both 129 substrains display higher levels of anxiety-like behaviour (conventional and/or ethological measures) relative to the C57BL/6JOlaHsd strain. Furthermore, all three inbred strains were less active in both tests when compared with the outbred Swiss-Webster strain. However, whereas C57BL/6JOlaHsd mice displayed lower levels of anxiety-like behaviour than their Swiss-Webster counterparts (both tests), 129S2/SvHsd (but not 129/SvEv) mice exhibited evidence of higher anxiety, particularly in the LDE test. The implications of these findings are discussed in relation to both the behavioural and pharmacological phenotyping of mutant mice.
 
The response of adrenal hormones and brain catecholamines to immobilization stress, applied in the morning or in the afternoon, was studied in rats. Immobilization induced greater increments in plasma corticosterone in the morning than in the afternoon; i.e. when the basal levels of this hormone were low rather than high. There was no significant difference between the plasma and adrenal corticosterone levels of the morning and those of the afternoon-stressed rats. Decreases in brain norepinephrine were observed in both groups (a.m. and p.m.) of immobilized rats, but no variations in dopamine concentration were detected. Immobilization led to a decline in the adrenal epinephrine level in the morning but no significant variation was observed in the afternoon-stressed rats.
 
Recent studies have shown that acute systemic administration of the selective orexin-1 receptor antagonist SB-334867 significantly reduces food intake in rats. Although this anorectic action of orexin-1 receptor blockade is associated with an acceleration in the transition from eating to resting, it is widely recognised that the behavioural indices of satiety are not dissimilar to those of illness. In this context, Experiment 1 confirmed a significant anorectic effect of 90 (but not 60) mg/kg lithium chloride (LiCl) in male rats presented with palatable mash in the home-cage environment. Experiment 2 employed a continuous monitoring technique to contrast the effects of LiCl (90 mg/kg) and SB-334867 (10 and 30 mg/kg) on food intake and behaviour during a 1-h test with palatable mash. SB-334867 dose-dependently inhibited food intake, with the higher dose producing a comparable degree of appetite suppression (approximately 40%) to that seen with LiCl. Despite equivalent anorectic action, the two compounds produced very different effects on behaviour. LiCl reduced active behaviours (locomotion, rearing, grooming and sniffing), slowed the rate of eating and disrupted the behavioural satiety sequence (BSS). In contrast, SB-334867 (30 mg/kg) decreased the duration of feeding and grooming, and modestly accelerated the transition between eating and resting. Furthermore, whereas LiCl failed to alter posttreatment bodyweight gain, SB-334867 (30 mg/kg) produced a significant weight loss in the 24-h period immediately following injection. Overall, the divergent profiles obtained with equianorectic doses of LiCl and SB-334867 provide convincing evidence for the behavioural selectivity of SB-334867-induced anorexia.
 
Mice of 129/J and C57BL/6J inbred strains received two-bottle, 48-h preference tests of NaCl solutions vs. distilled water. 129/J mice exhibited a greater preference for 0.08 M NaCl than did C57BL/6J mice. To determine if this strain difference was mediated by taste, the integrated neural responses of the chorda tympani nerve to a concentration range of NaCl and KCl were examined. Gustatory neural responses to NaCl were similar for 129/J and C57BL/6J mice. However, lingual application of 0.5 mM amiloride hydrochloride significantly suppressed chorda tympani responses to a range of NaCl concentrations in C57BL/6J mice but did not do so consistently in 129/J mice. Amiloride failed to significantly suppress responses to a range of KCl concentrations in both mouse strains. The results suggest that for 129/J mice, sodium reception and transduction are primarily amiloride insensitive, whereas for C57BL/6J mice, both amiloride-sensitive and amiloride-insensitive components are present. The strain difference in NaCl intake may be mediated, in part, through gustatory mechanisms, with reduced preference for NaCl influenced by amiloride-sensitive sodium transduction mechanisms.
 
Purified carbohydrates and fats are usually palatable to humans and other animals, and their consumption often induces weight gain and accumulation of fat. In this study, we examined consumption of complex carbohydrates (cornstarch and Polycose) and fats (soybean oil and margarine) in mice from two inbred strains, C57BL/6ByJ and 129P3/J. At lower concentrations of liquid nutrients tested using two-bottle tests, when the amounts consumed had negligible energy content, the C57BL/6ByJ mice had higher acceptance of Polycose and soybean oil. This was probably due to strain differences in chemosensory perception of Polycose and oil. At higher concentrations, the mice consumed a substantial part of their daily energy from the macronutrient sources, however, there were no or only small strain differences in nutrient consumption. These small differences were probably due to strain variation in body size. The two strains also did not differ in chow intake. Despite similar energy intakes, access to the nutrients resulted in greater body weight (BW) gain in the C57BL/6ByJ mice than in the 129P3/J mice. The diet-induced weight gain was examined in detail in groups of 2-month-old C57BL/6ByJ and 129P3/J mice given ether chow, or chow and margarine to eat. Access to margarine did not increase total energy consumption of either strain. It increased BW and adiposity of the C57BL/6ByJ mice, but only after they reached the age of approximately 3 months. There were no differences in BW and adiposity between control and margarine-exposed 129P3/J mice. The results suggest that diet-induced adiposity in the B6 mice depends on age and does not depend on hyperphagia.
 
Prior research with inbred mouse strains indicates that C57BL/6J (B6) mice display stronger preference and acceptance for various sweeteners than do 129P3/J (129) mice. Experiment 1 examined the extent to which this strain difference could be modified by repeated exposure to sucrose. Sucrose-naive 129 mice displayed weaker preferences than did B6 mice for 0.5% to 4% sucrose solutions during 23h/day sugar vs. water tests. Sucrose preference did not differ at 8-32% concentrations. Yet, when retested with sucrose, the 129 and B6 mice showed identical robust preferences (>90%) for 0.5-32% solutions. The strains also did not differ in sucrose preference in tests with descending sucrose concentrations (0.5-0.0625%). Sucrose-experienced 129 mice also showed enhanced preference for dilute saccharin solutions suggesting that their sweet taste responsivity was enhanced. Experiment 2 revealed that preference for dilute saccharin solutions was enhanced by prior saccharin experience in B6 but not 129 mice. Experiment 3 tested the strains with Polycose which has a palatable taste different from that of sucrose. Polycose-naive 129 mice displayed weaker preferences for dilute (0.5-4%) but not concentrated (8-32%) Polycose solutions relative to B6 mice. In the second test series Polycose preferences were nearly identical in the two strains. In Experiments 1 and 3, prior sucrose or Polycose experience also reduced or eliminated strain differences in saccharide acceptance (absolute intake) at higher but not lower concentrations. Thus, exposure to the oral and post-oral actions of sucrose and Polycose increased saccharide preference in B6 mice and even more in 129 mice so that the strain difference virtually disappeared. Whether the 129 mice responded to the taste or other properties (e.g., odor) of the dilute saccharide solutions is not certain but their gustatory sensitivity needs to be reconsidered.
 
As compared to C57BL/6J mice, 129P3/J mice show weaker preferences for and lower intakes of dilute sugar solutions. These differences have been attributed to genetic differences in their sweet taste receptor. The two mouse strains do not differ, however, in their intake of concentrated sugar solutions. The post-oral satiating effect of concentrated sugar solutions may mask strain differences in the avidity for these solutions. This hypothesis was investigated using fixed ratio (FR, low demand) and progressive ratio (PR, high demand) operant licking tests (22h/day) to measure sugar appetite. In Experiment 1, sucrose-experienced 129 mice licked less than did B6 mice for 4% but not for 16% sucrose in free access bottle tests and FR operant tests. Yet, in PR tests the 129 mice licked as much for 4% sucrose and more for 16% sucrose than did B6 mice. In Experiment 2, sucrose-naive 129 mice licked less than did B6 mice in FR and PR tests with 0.4% saccharin but the strains did not differ in PR licking in their first test with 16% sucrose. After they were given unconstrained bottle access to 16% sucrose for 3 days, the 129 mice now licked more than B6 mice in a second sucrose PR test. Thus, despite having a less sensitive sweet taste receptor, 129 mice are as much or more motivated to obtain sucrose than are B6 mice and appear to be more influenced by prior experience with sugar. This suggests that the strains differ in their central reward processing of sweet taste.
 
Top-cited authors
Anthony Sclafani
  • City University of New York - Brooklyn College
Barbara Jean Rolls
  • Pennsylvania State University
John de Castro
  • Sam Houston State University
Tony Yaksh
  • University of California, San Diego
Linda M Bartoshuk
  • University of Florida