-
[show abstract]
[hide abstract]
ABSTRACT: Evidence shows that maternal care and postnatal traumatic events can exert powerful effects on brain circuitry development but little is known about the impact of early postnatal experiences on processing of rewarding and aversive stimuli related to the medial prefrontal cortex (mpFC) function in adult life. In this study, the unstable maternal environment induced by repeated cross-fostering (RCF) impaired palatable food conditioned place preference and disrupted the natural preference for sweetened fluids in the saccharin preference test. By contrast, RCF increased sensitivity to conditioned place aversion (CPA) and enhanced immobility in the forced swimming test. Intracerebral microdialysis data showed that the RCF prevents mpFC dopamine (DA) outflow regardless of exposure to rewarding or aversive stimuli, whereas it induces a strong and sustained prefrontal norepinephrine (NE) release in response to different aversive experiences. Moreover, the selective mpFC NE depletion abolished CPA, thus indicating that prefrontal NE is required for motivational salience attribution to aversion-related stimuli. These findings demonstrate that an unstable maternal environment impairs the natural propensity to seek pleasurable sources of reward, enhances sensitivity to negative events in adult life, blunts prefrontal DA outflow, and modulates NE release in the reverse manner depending on the exposure to rewarding or aversive stimuli.
Cerebral Cortex 06/2012; · 6.54 Impact Factor
-
Roberta Possenti,
Giampiero Muccioli,
Pamela Petrocchi,
Cheryl Cero,
Aderville Cabassi,
Lucy Vulchanova,
Maureen S Riedl,
Monia Manieri,
Andrea Frontini,
Antonio Giordano, [......],
Antonio Torsello,
Vittorio Locatelli,
Valentina Sanghez,
Bjarne D Larsen,
Jorgen S Petersen,
Paola Palanza,
Stefano Parmigiani, Anna Moles,
Andrea Levi,
Alessandro Bartolomucci
[show abstract]
[hide abstract]
ABSTRACT: The peptides encoded by the VGF gene are gaining biomedical interest and are increasingly being scrutinized as biomarkers for human disease. An endocrine/neuromodulatory role for VGF peptides has been suggested but never demonstrated. Furthermore, no study has demonstrated so far the existence of a receptor-mediated mechanism for any VGF peptide. In the present study, we provide a comprehensive in vitro, ex vivo and in vivo identification of a novel pro-lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity for TLQP-21 was higher in the WAT as compared with other tissues, and selectively up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in murine adipocytes via a mechanism encompassing the activation of noradrenaline/β-adrenergic receptors pathways and dose-dependently decreases adipocytes diameters in two models of obesity. In conclusion, we demonstrated a novel and previously uncharacterized peripheral lipolytic pathway encompassing the VGF peptide TLQP-21. Targeting the sympathetic nerve-adipocytes interaction might prove to be a novel approach for the treatment of obesity-associated metabolic complications.
Biochemical Journal 08/2011; 441(1):511-22. · 4.90 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mice born from high care-giving females show, as adults, low anxiety levels, decreased responsiveness to stress, and substantial improvements in cognitive function and hippocampal plasticity. Given the relevance of this issue for preventing emotional and cognitive abnormalities in high-risk subjects, this study examines the possibility to further enhance the beneficial effects observed in the progeny by augmenting maternal care beyond the highest levels females can display in standard laboratory conditions. This was produced by placing a second female with the dam and its litter in the rearing cage from the partum until pups weaning. Maternal behavior of all females was scored during the first week postpartum, and behavioral indices of emotionality, prestress and poststress corticosterone levels, cognitive performance, and hippocampal morphology were assessed in the adult offspring. We found that pups reared by female dyads received more maternal care than pups reared by dams alone, but as adults, they did not exhibit alterations in emotionality or corticosterone response estimated in basal condition or following restraint stress. Conversely, they showed enhanced performance in hippocampal-dependent tasks including long-term object discrimination, reactivity to spatial change, and fear conditioning together with an increase in dendritic length and spine density in the CA1 region of the hippocampus. In general, the beneficial effects of dyadic maternal care were stronger when both the females were lactating. This study demonstrates that double-mothering exerts a long-term positive control on cognitive function and hippocampal neuronal connectivity. This experimental manipulation, especially if associated with increased feeding, might offer a concrete possibility to limit or reverse the consequences of negative predisposing conditions for normal cognitive development.
Hippocampus 03/2011; 21(3):298-308. · 5.18 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The opioid system controls social behavior and it was hypothesized that it therefore plays a role in neuropsychiatric disorders such as autism that are characterized by social and communication deficits. Mice communicate via ultrasonic vocalizations. As pups, they produce ultrasonic vocalizations when isolated from dam and littermates. These calls serve an important biological purpose, since they elicit search and retrieval behavior in the mother. Administration of μ-opioid-receptor-agonists diminishes such isolation-induced ultrasonic vocalizations and μ-opioid-receptor knock-out mouse pups (Orpm(-/-)) emit fewer ultrasonic vocalizations during isolation than intact controls (Orpm(+/+)). In adulthood, male and female mice produce ultrasonic vocalizations during social interactions. However, little is known about occurrence and function of ultrasonic vocalizations produced by adult females. Here, we conducted a playback experiment in order to assess whether female ultrasonic vocalizations elicit changes in the recipient's behavior and whether a possible change in behavior is dependent on a functioning opioid system by comparing Orpm(-/-) mice with Orpm(+/+) controls. Our results showed that female ultrasonic vocalizations elicit exploratory activity in male recipients and that elicitation of exploratory activity in response to female ultrasonic vocalizations is dependent on an intact opioid system, since such a response was not seen in Orpm(-/-) mice. Lack of exploratory activation seen in Orpm(-/-) mice is unlikely due to hearing deficits as shown by an auditory cued fear-conditioning-task. Hence, these findings support the phenotypic relevance of Orpm(-/-) mice for the study of autism.
Social neuroscience 02/2011; 6(1):76-87. · 3.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A large body of evidence links altered opioid signaling with changes in social behavior in animals. However, few studies have attempted to determine whether similar links exist in humans. Here we investigate whether a common polymorphism (A118G) in the mu-opioid receptor gene (OPRM1) is associated with alterations in personality traits linked to affiliative behavior and attachment. In a mixed sample (N = 214) of adult healthy volunteers and psychiatric patients, we analyzed the association between the A118G polymorphism of the OPRM1 and two different psychological constructs reflecting individual differences in the capacity to experience social reward. Compared to individuals expressing only the major allele (A) of the A118G polymorphism, subjects expressing the minor allele (G) had an increased tendency to become engaged in affectionate relationships, as indicated by lower scores on a self-report measure of avoidant attachment, and experienced more pleasure in social situations, as indicated by lower scores on a self-report measure of social anhedonia. The OPRM1 variation accounted for about 3.5% of the variance in the two measures. The significant association between the A118G polymorphism and social hedonic capacity was independent of the participants' mental health status. The results reported here are in agreement with the brain opioid hypothesis of social attachment and the established role of opioid transmission in mediating affiliative behavior.
Social neuroscience 02/2011; 6(1):88-97. · 3.17 Impact Factor
-
Francesca R D'Amato,
Claudio Zanettini,
Valentina Lampis,
Roberto Coccurello,
Tiziana Pascucci,
Rossella Ventura,
Stefano Puglisi-Allegra,
Chiara A M Spatola,
Paola Pesenti-Gritti,
Diego Oddi, Anna Moles,
Marco Battaglia
[show abstract]
[hide abstract]
ABSTRACT: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO(2) hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO(2) through genetic control of sensitivity to the environment.
Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O(2)), CO(2)-enriched air (6% CO(2)), hypoxic air (10%O(2)), and avoidance of CO(2)-enriched environments.
Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO(2)-enriched air and heightened aversion towards CO(2)-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO(2) was present at 16-20, and 75-90 postnatal days, implying the trait's stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO(2) breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO(2) increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals.
A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO(2) sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.
PLoS ONE 01/2011; 6(4):e18637. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Beside the therapeutic improvement over first-generation antipsychotics, the fact that prescription of atypical agents is also associated to the emergence of severe metabolic derangement in patients is not a mystery anymore. Body weight gain, dyslipidemia, adiposity, impaired glucose homeostasis, insulin and leptin resistance and new-onset type II diabetes are all part of a syndromic cluster of vast medical concern. Thus, clinical reports and rodent models of atypical antipsychotic-associated metabolic impairment have growth in parallel as separate territories. This review focuses on the attempt to take a snapshot of the present developing moment and to describe to what extent clinical data are reflected by the findings derived from animal studies. This aim is pursued through different steps that, starting from the criteria necessary to characterize the "atypicality" of atypical drugs, then explore the consistency among clinical and animal-based data. The endpoint of this survey consists in the analysis of the potential mechanisms underlying the metabolic derangement induced by this class of drugs. It is, indeed, our opinion that some atypical antipsychotics should be viewed as potent obesogenic factors that can be exploited as valuable tools to shed light into the elusive dilemma of obesity. For this reason, recently identified obesogenic and diabetogenic mechanisms are the background on which the present work is built and some novel forthcoming lines of investigation suggested.
Pharmacology [?] Therapeutics 09/2010; 127(3):210-51. · 8.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In comparison with conventional, first-generation antipsychotics (e.g., haloperidol), the administration of atypical antipsychotics (AAPs) has been associated with a higher risk of metabolic derangements, including body weight increase, dysregulation of glucose homeostasis, fat accumulation, and even liability to develop type II diabetes. Since this is a serious clinical problem that may be further exacerbated in overweight schizophrenics, establishing animal models of AAP-induced adverse effects may contribute to clarifying the mechanisms underlying these effects. Here we present three basic protocols by which this problem has been modeled. The three protocols differ in many aspects (routes of administration, extent of the chronic treatment, diets, and dosage regimen), and the pros and cons of each procedure are systematically detailed throughout. It should be noted that several factors (e.g., species, sex, duration, and class of AAPs) could restrict the feasibility of these models, as well as their correspondence to the clinical condition.
Current protocols in neuroscience / editorial board, Jacqueline N. Crawley ... [et al.] 07/2010; Chapter 9:Unit9.33.
-
[show abstract]
[hide abstract]
ABSTRACT: Neurons detect free fatty acids (FFAs) availability and use this nutritional status to modulate feeding and control body weight.
The work is designed to characterize the impact on feeding behavior of either oleic acid (OA) administration (experiment 1) or the inhibition (experiment 2) of the enzyme carnitine palmitoyltransferase-1 (CPT-1). The structure of feeding behavior and satiation time course were examined through the behavioral satiety sequence (BSS) paradigm.
Adult male mice were initially habituated to a palatable diet, then subjected to intracerebroventricular (i.c.v.) infusion of different doses of OA or the CPT-1 inhibitor ST1326. Food intake at different time points, duration, and frequencies of feeding and non-feeding-related behaviors were continuously monitored over 40 min and satiety development profiled according to BSS.
Intra-i.c.v. infusion of oleic acid (300 nM) and ST1326 (50 and 75 pM) suppressed food intake. As indicated by the earlier leftward shifting of the normal transition from eating to resting, both strategies similarly accelerated the onset of satiety. The premature onset of satiety resulted in a dose-related fashion with 50 pM of ST1326 producing a marked premature onset than the lower dose. However, at the highest dose injected, the inhibition of CPT-1 disrupted the BSS profile.
The increased neuronal availability of FFAs mediates a significant anorectic response which is mirrored by an early occurrence of satiety onset. Besides supporting the role of central nutrient sensing in feeding, the present data demonstrate that the modulation of satiety enhancement can produce appetite suppressant effects within narrow range of neuronal FFAs availability.
Psychopharmacologia 03/2010; 210(1):85-95. · 4.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this study was to model in mice the association between metabolic syndrome and the administration of atypical antipsychotic (AAP). Two dosages (4 and 8 mg/kg per day) of olanzapine (OL) were infused in 36 female mice for 30 days by osmotic mini-pumps. This study was also designed to further extend the implications raised in other experiments by our model of AAP-induced metabolic dysregulation. Through the use of the osmotic mini-pumps, this model is aimed to circumvent the shorter (than in humans) half-life of AAPs in rodents and to chronically administer OL by a reliable and less disturbing method. Indirect calorimetry was used to evaluate metabolic rate (MR) and respiratory exchange ratio together with weight and caloric intake. Serum insulin, leptin, and glucose tolerance (oral glucose tolerance test) were assessed. Pancreatic beta cells insulin levels, periuterine and liver fat content were also analyzed. Olanzapine-infused mice exhibited a reduction of overall MR (kilojoule per hour) and resting MR and respiratory exchange ratio, with periuterine fat significantly enlarged. All metabolic alterations were detected at the highest dose, with major effects found on weight gain and hyperphagia. Impaired glucose metabolism, associated with hyperinsulinemia and hyperleptinemia were found. Insulin resistance was evidenced by the raise of HOMA-IR index. Increased insulin and lipid storage were detected at pancreatic and hepatic levels respectively. These findings illustrate the development of a cluster of risk factors (metabolic syndrome) and, for the first time, a decrease of energy expenditure (MR) due to chronic OL infusion.
Journal of clinical psychopharmacology 12/2009; 29(6):576-83. · 5.09 Impact Factor
-
Alessandro Bartolomucci,
Elena Bresciani,
Ilaria Bulgarelli,
Antonello E Rigamonti,
Tiziana Pascucci,
Andrea Levi,
Roberta Possenti,
Antonio Torsello,
Vittorio Locatelli,
Eugenio E Muller, Anna Moles
[show abstract]
[hide abstract]
ABSTRACT: The vgf gene regulates energy homeostasis and the VGF-derived peptide TLQP-21 centrally exerts catabolic effects in mice and hamsters. Here, we investigate the effect of chronic intracerebroventricular (icv) injection of TLQP-21 in mice fed high fat diet (HFD). Fast weight-gaining mice injected with the peptide or cerebrospinal fluid were selected for physiological, endocrine, and molecular analysis. TLQP-21 selectively inhibited the increase in body weight and epididymal white adipose tissue (eWAT) weight induced by HFD in control animals despite both groups having a similar degree of hyperphagia. TLQP-21 normalized the increase in leptin and decrease in ghrelin while increasing epinephrine and epinephrine/norepinephrine ratio when compared to values in controls. Finally, HFD-TLQP-21 mice showed a selective increase of eWAT beta3-adrenergic receptor mRNA. Peroxisome-proliferator-activated-receptor-delta and hormone-sensing-lipase mRNA were also upregulated. In conclusion, chronic icv infusion of TLQP-21 prevented the early phase of diet-induced obesity despite overfeeding. These effects were paralleled by activation of catabolic pathways within the eWAT. Our results further support a role for TLQP-21 as a catabolic neuropeptide.
Genes & Nutrition 03/2009; 4(1):49-57. · 2.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Vgf, is a neuro-endocrine specific gene encoding for a large protein precursor of different peptides. A role for VGF in pain modulation has been suggested from immunohistochemical studies showing VGF mRNA widely expressed in primary sensory neurons. In this study, the presence of VGF on the primary sensory afferents in mice was confirmed by showing its immunostaining in cultured neurons of dorsal root ganglia in secretory granule varicosities colocalized with Substance P. Moreover, the functional role of a C-terminal internal VGF-derived peptide, i.e. TLQP-21, was assessed by investigating its peripheral (1, 2, 4, 8mM) and central (1, 2, 4 mM) effects on inflammatory pain in the formalin test. A significant increase of pain-related licking response following peripheral injection of TLQP-21 (4 and 8mM) was observed in the second inflammatory phase of the test. In addition, an increase in licking response was detected when 4 mM of the peptide was injected alone without formalin. On the other hand, the central administration of TLQP-21 induced an U-shaped curve, with the dose of 2 mM being analgesic during the second phase. This study shows for the first time that a VGF-derived peptide may be involved in inflammatory pain in vivo and demonstrates a different action for TLQP21 at the peripheral and central levels of the nociceptive pathways.
Neuroscience Letters 09/2008; 441(1):129-33. · 2.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A mouse model of atypical antipsychotic-associated adverse effects was used to compare the liability to induce weight gain, food intake, and metabolic alterations after chronic olanzapine (OL; LY170053, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno-[2,3-b][1,5] benzodiazepine) and ST2472 (ST; 9-piperazin-1-ylpyrrolo[2,1-b][1,3]benzothiazepine) administration. By adding two equipotent doses (3 and 6 mg/kg) of either OL or ST to a high-sweet, high-fat (HS-HF) diet, mice were allowed to self-administer drugs up to 50 days. Body weight and food intake were evaluated daily. Locomotor activity was recorded over 48 h at two different time points. Dyslipidemia was measured by central visceral obesity. Blood serum levels of insulin (IN), glucose (Glu), triglycerides (TGs), nonesterified fatty acids (NEFAs), cholesterol (Ch), and ketone (Ke) bodies were quantified. OL treatment at 3 mg/kg enhanced body weight, whereas at the highest dose, the increase became evident only during the last 10 days of treatment. OL (3 mg/kg) increased HS-HF intake over time, whereas the highest dose reduced intake during the second 10 and final 10 days of administration. Both compounds induced nocturnal hypomotility at the highest dose. In contrast to ST, 3 mg/kg OL elevated serum levels of IN, Glu, TG, NEFA, Ch, and Ke, whereas 6 mg/kg OL elevated those of Glu, TG, and Ch. In contrast, ST did not affect weight gain, food intake, and metabolic markers. Given the similarities between OL-induced obesogenic effects and medical reports, this study further supports the view that ST may represent a new class of agents characterized by a low propensity to induce side effects with promising clinical safety.
Journal of Pharmacology and Experimental Therapeutics 07/2008; 326(3):905-11. · 3.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Obesity is a current health pandemia. Determinants of this pathology are rather complex and include genetic, developmental and environmental factors only partially disclosed. Stress related neuroendocrine dysregulation and overconsumption of high palatable high caloric food and are likely to contribute to this modern health threats. Despite the evidence that psychosocial stress is one of the main sources of stress in humans and may play an important role in the development of the stress disorders, including obesity and metabolic syndrome, animal models focusing on the relationship between chronic stress and energy homeostasis are scattered and most of them encompasses physical rather than psychosocial stress. Aim of the present paper is to review rodent studies on the effect of psychosocial stress throughout life on body weight and food intake regulation. In the second part of the review special focus will be given on the mechanisms linking stress and the reward system.
Neuroscience & Biobehavioral Reviews 06/2008; 33(4):537-50. · 8.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Energy homeostasis is a complex physiological function coordinated at multiple levels. The issue of genetic regulation of nutrition and metabolism is attracting increasing interest and new energy homeostasis-regulatory genes are continuously identified. Among these genes, vgf is gaining increasing interest following two observations: (1) VGF-/- mice have a lean and hypermetabolic phenotype; (2) the first VGF-derived peptide involved in energy homeostasis, named TLQP-21, has been identified. The aim of this review will be to discuss the role of the vgf gene and VGF derived peptides in metabolic and nutritional functions. In particular we will: (1) provide a brief overview on the central systems regulating energy homeostasis and nutrition particularly focusing on the melanocortin system; (2) introduce the structure and molecular characteristic of vgf; (3) describe the phenotype of VGF deficient mice; (4) present recent data on the metabolic role of VGF-derived peptides, particularly focusing on one peptide named TLQP-21.
Genes & Nutrition 12/2007; 2(2):169-80. · 2.51 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Despite the evidence that ultrasonic vocalizations are a consistent component of the behavioural repertoire of female mice, only few studies have investigated this phenomenon. In this paper, we reported new data about ultrasonic vocalisations emitted during female-female mice social encounters. In particular, we first showed that the resident female utters a considerable number of 70 kHz calls and that the number of calls seems to be modulated by the motivational state of the emitter during the estrous cycle: sexually receptive females emitted fewer ultrasonic vocalizations than non-receptive ones in the presence of a female intruder. A strong positive correlation linked the number of calls and the time spent by the resident sniffing the intruder female. Moreover, the number of calls uttered during interaction with an unknown female partner significantly decreased with pregnancy and ageing. Secondly we reported that 1-year-old female mice showed a reduction of ultrasonic calls in the presence of a partner they had been exposed to, only if the re-exposure (test) occurred 30 min after the previous presentation. If the test was performed with a delay of 60 min, the number of calls emitted did not decrease. These results confirm that ultrasonic vocalizations emitted during social interaction with a female conspecific can be used as an index of social recognition and can be useful to detect age-related disruption of social memory in female mice.
Behavioural Brain Research 10/2007; 182(2):223-30. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Social responses are a key element for behavioral phenotyping of mouse models of neurodevelopmental disorders associated with social deficits. Here we describe selected behavioral responses that can be measured in developing and adult mice, with special emphasis on ultrasonic vocalizations, a behavioral response not yet systematically characterized in most of the genetic mouse models of social abnormalities. A recently developed task to measure social approach relevant to the first core symptom of autism is highlighted. We also focus on those developmental factors, including litter size, litter composition, and early social milieu, that are often underestimated when measuring adult social behavior in mouse models of neurodevelopmental disorders. We present a summary of available data concerning social behavioral responses in mice with targeted gene mutations. We conclude by suggesting that assessment of early behavioral traits, and corresponding relationships with adult behavioral profiles, could be a useful strategy to investigate mouse models of neurodevelopmental disorders associated with social deficits.
Behavioural Brain Research 02/2007; 176(1):40-52. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In rats and mice, the ultrasonic vocalizations emitted by pups have been suggested to modulate maternal behavior. In the present study we show that the number of calls emitted by mouse pups can reflect maternal responsiveness. Maternal responsiveness towards pups was evaluated on postnatal day 8 using a three-compartment cage test where the mother, to reach the pups, had to cross the central part of the cage containing cues from a potentially infanticidal male. Maternal responsiveness was lower when alien rather than own pups were used as stimulus. Moreover, the administration of morphine (2.5 mg/kg, i.p.) a drug known to disrupt maternal behavior, resulted in an increase of the latency to reach the pups, as well. This behavioral and pharmacological validation supports the hypothesis that this measure can represent an index of maternal motivation. Therefore, we evaluated maternal responsiveness on day 8 postpartum and pups' ultrasound emission during isolation on day 4 and 8 of life, under conditions strongly affecting the amount of maternal behavior received by pups. C57BL/6 mothers scored higher in maternal responsiveness than BALB/c females, and their pups emitted fewer calls than BALB/c pups both on days 4 and 8. Mothers of handled pups scored higher than controls in maternal responsiveness. Handled pups showed a lower rate of calls on day 8, although they did not differ from controls on day 4. These results support our hypothesis that maternal responsiveness, that is mother promptness to respond to pups' needs, is one of the factors tuning the rate of ultrasonic emission of the offspring.
Behavior Genetics 02/2005; 35(1):103-12. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In rats and mice, the ultrasonic vocalizations emitted by pups have been suggested to modulate maternal behavior. In the present study we show that the number of calls emitted by mouse pups can reflect maternal responsiveness. Maternal responsiveness towards pups was evaluated on postnatal day 8 using a three-compartment cage test where the mother, to reach the pups, had to cross the central part of the cage containing cues from a potentially infanticidal male. Maternal responsiveness was lower when alien rather than own pups were used as stimulus. Moreover, the administration of morphine (2.5mg/kg, i.p.) a drug known to disrupt maternal behavior, resulted in an increase of the latency to reach the pups, as well. This behavioral and pharmacological validation supports the hypothesis that this measure can represent an index of maternal motivation. Therefore, we evaluated maternal responsiveness on day 8 postpartum and pups ultrasound emission during isolation on day 4 and 8 of life, under conditions strongly affecting the amount of maternal behavior received by pups. C57BL/6 mothers scored higher in maternal responsiveness than BALB/c females, and their pups emitted fewer calls than BALB/c pups both on days 4 and 8. Mothers of handled pups scored higher than controls in maternal responsiveness. Handled pups showed a lower rate of calls on day 8, although they did not differ from controls on day 4. These results support our hypothesis that maternal responsiveness, that is mother promptness to respond to pups needs, is one of the factors tuning the rate of ultrasonic emission of the offspring.
Behavior Genetics 12/2004; 35(1):103-112. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In the present study we examined the long-term effects of neonatal lesion of basal forebrain cholinergic neurons induced by intracerebroventricular injections of the immunotoxin 192 IgG saporin. Animals were then characterised behaviourally, electrophysiologically and molecularly. Cognitive effects were evaluated in the social transmission of food preferences, a non-spatial associative memory task. Electrophysiological effects were assessed by recording of cortical electroencephalographic (EEG) patterns. In addition, we measured the levels of proteins whose abnormal expression has been associated with neurodegeneration such as amyloid precursor protein (APP), presenilin 1 and 2 (PS-1, PS-2), and cyclooxygenases (COX-1 and COX-2). In animals lesioned on postnatal day 7 and tested 6 months thereafter, memory impairment in the social transmission of food preferences was evident, as well as a significant reduction of choline acetyltransferase activity in hippocampus and neocortex. Furthermore, similar to what observed in Alzheimer-like dementia, EEG cortical patterns in lesioned rats presented changes in alpha, beta and delta activities. Levels of APP protein and mRNA were not affected by the treatment. Levels of hippocampal COX-2 protein and mRNA were significantly decreased whereas COX-1 remained unaltered. PS-1 and PS-2 transcripts were reduced in hippocampus and neocortex. These findings indicate that neonatal and permanent basal forebrain cholinergic hypofunction is sufficient to induce behavioural and neuropathological abnormalities. This animal model could represent a valid tool to evaluate the role played by abnormal cholinergic maturation in later vulnerability to neuropathological processes associated with cognitive decline and, possibly, to Alzheimer-like dementia.
Experimental Neurology 10/2004; 189(1):162-72. · 4.70 Impact Factor
