Sugar-dependent rats show enhanced responding for sugar after abstinence: Evidence of a sugar deprivation effect
ABSTRACT Studies have shown that intermittent sugar availability (12 h/day) produces signs of dependence in rats, including escalation of intake, mu-opioid and dopamine receptor changes, behavioral and neurochemical indices of withdrawal, and cross-sensitization with amphetamine. "Deprivation-effect" paradigms, whereby abstinence from a substance results in enhanced intake, are often used to measure "craving" for drugs of abuse, such as alcohol. The present study used operant conditioning to investigate consumption of sugar after abstinence in rats selected for glucose avidity. The experimental group was trained on a fixed ratio (FR-1) schedule for 25% glucose for 30 min/day for 28 days and also had glucose access in the home cages for an additional 11.5 h daily. The control group had only the 30-min/day access to glucose in the operant chambers. Then, both groups were deprived of glucose for 2 weeks. After this period of abstinence, animals were put back in the operant chambers. The experimental group responded significantly more than ever before, and significantly more than the control group. In conclusion, daily 12-h access to sugar, in the paradigm used, can result in an altered neural state that lasts throughout 2 weeks of abstinence, leading to enhanced intake. Together with previous results, this deprivation effect supports the theory that animals may become dependent on sugar under selected dietary circumstances.
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- "In agreement with this idea, adult C57BL/6J mice exposed to IAA escalate EtOH consumption and achieve high stable levels of EtOH drinking after 3 weeks, followed by initial signs of withdrawal (Hwa et al., 2011). In fact, intermittency appears to be a crucial feature of many conditions that promote ingestive behavior, including increasing amounts of EtOH (Avena et al., 2005; Falk and Tang, 1988; Sinclair and Senter, 1968). In the present study, 2 procedures of drinking promoted similarly high BECs after 4-hour access to 20% EtOH. "
ABSTRACT: Background Most studies with corticotropin releasing factor (CRF) and ethanol (EtOH) consumption have focused on CRF type 1 (CRF1) receptors; less is known about other components of the CRF system, such as the CRF type 2 (CRF2) receptors and the CRF binding protein (CRFBP). In humans, several nucleotide polymorphisms in the CRFBP gene have been associated with EtOH abuse.Methods The role of the CRFBP within the ventral tegmental area (VTA) and the central nucleus of the amygdala (CeA) was investigated in C57BL/6J mice exposed to an EtOH binge drinking paradigm (drinking in the dark [DID]), or to a dependence-producing drinking protocol (2-bottle choice, intermittent access to alcohol [IAA]) for 4 weeks. Potential interactions between VTA CRFBP and CRF2 receptors on EtOH binge drinking were also assessed. Mice were microinjected with the CRFBP antagonist CRF fragment 6–33 (CRF6–33) into the VTA or CeA, or with the CRF2 antagonist astressin-2B (A2B) alone or in combination with CRF6–33 into the VTA, and had access to 20% (w/v) EtOH for 4 hours (DID). Separate cohorts of mice received vehicle and doses of CRF6–33 into the VTA or CeA and had access to EtOH/water for 24 hours (IAA). Blood EtOH concentrations (BECs) were measured, and signs of withdrawal by handling-induced convulsions were determined.ResultsIntra-VTA CRF6–33 and A2B reduced EtOH intake dose dependently in mice during DID. Furthermore, a combination of a subeffective dose of CRF6–33 and a lower dose of A2B promoted additive effects in attenuating EtOH binge drinking. Intra-VTA CRF6–33 did not affect EtOH consumption in mice given IAA, and intra-CeA CRF6–33 did not change alcohol consumption in both models of drinking. DID and IAA promoted pharmacologically relevant BECs; however, only mice given IAA exhibited convulsive events during withdrawal.Conclusions These findings suggest that VTA CRFBP is involved in the initial stages of escalated EtOH drinking by mechanisms that may involve CRF2 receptors.Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12825 · 3.31 Impact Factor
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- "It has been demonstrated that fasting may increase the intake of palatable foods and drugs (Avena et al., 2005). Corroborating this study, after 12 h of fasting, we demonstrated that the offspring with access to palatable diets (C- SSD and S-SSD) had greater food intake after 30 min, suggesting greater voracity than that displayed by the groups that only had access to the SC (C-SC and S- SC). "
ABSTRACT: Children from pregnant smokers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption. Here, we studied the relationship between tobacco smoke exposure during lactation with feeding, behavior and brain dopaminergic reward system parameters at adulthood. Nursing Wistar rats and their pups were divided into two groups: tobacco smoke-exposed (S: 4 times/day, from the 3(rd) to the 21(th) day of lactation), and ambient air-exposed (C). On PN175, both offspring groups were subdivided for a food challenge: S and C that received standard chow (SC) or that chose between high-fat (HFD) and high-sucrose diets (HSD). Food intake was recorded after 30 min and 12 h. Offspring were tested in the elevated plus maze and open field on PN178-179; they were euthanized for dopaminergic analysis on PN180. SSD (self-selected diet) animals presented a higher food intake compared to SC ones. S-SSD animals ate more than C-SSD ones at 30 min and 12 h. Both groups preferred the HFD. However, S-SSD animals consumed relatively more HFD than C-SSD at 30 min. No behavioral differences were observed between groups. S animals presented lower tyrosine hydroxylase (TH) content in the ventral tegmental area, lower TH, dopaminergic receptor 2, higher dopaminergic receptor 1 contents in the nucleus accumbens and lower OBRb in hypothalamic arcuate nucleus. Tobacco-smoke exposure during lactation increases preference for fat in the adult progeny possibly due to alterations in the dopaminergic system. Copyright © 2015. Published by Elsevier Ltd.Neuroscience 06/2015; 301. DOI:10.1016/j.neuroscience.2015.06.001 · 3.33 Impact Factor
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- "In fact, studies have revealed substantial overlap between the brain circuitry underlying addictive behaviors and overeating; for instance, both substance-dependent and obese subjects exhibit decreased reward circuit activation in response to the drug of choice or palatable foods (Stice et al., 2008; Tomasi and Volkow, 2013; Volkow et al., 2013). Rats have also been found to self-administer sugar in ways which resemble substance abuse, involving loss of control, cross tolerance, failed attempts to quit, and the spontaneous production of withdrawal signs and symptoms following opiate antagonist administration (Avena et al., 2005; Gold and Avena, 2013; Hoebel et al., 2009). One factor which has been recently found to influence food preferences and eating behavior over the life-course is fetal/neonatal history (Portella et al., 2012; Silveira et al., 2006b, 2004, 2008). "
ABSTRACT: Early handling alters adult behavioral responses to palatable food and to its withdrawal following a period of chronic exposure. However, the central mechanisms involved in this phenomenon are not known. Since neonatal handling has persistent effects on stress and anxiety responses, we hypothesized that its involvement in the aforementioned association may be associated with differential neuroadaptations in the amygdala during withdrawal periods. Litters were randomized into two groups: handled (H, removed from their dam for 10min per day from the first to the tenth postnatal day and placed in an incubator at 32°C) and non-handled (NH). Experiment 1: on PNDs 80-100, females were assigned to receive palatable food+rat chow for 15 or 30 days, and these two groups were compared in terms of palatable food preference, body weight and abdominal fat deposition. In Experiment 2, H and NH rats were exposed to a chronic diet of palatable food+rat chow for 15 days, followed by (a) no withdrawal, (b) 24h withdrawal from palatable food (receiving only rat chow) or (c) 7-day withdrawal from palatable food (receiving only rat chow). Body weight, 10-min rebound palatable food intake, abdominal fat deposition, serum corticosterone as well as TH and pCREB levels in the amygdala were then compared between groups. Experiment 1-chronic exposure to palatable food induces comparable metabolic effects after 15 and 30 days. Experiment 2-neonatal handling is associated with a peculiar response to palatable food withdrawal following chronic exposure for 15 days. Rats exposed to early handling ingested less of this food after a 24h withdrawal period, and displayed increased amygdala TH and pCREB levels. Variations in the neonatal environment affect both behavioral responses and amygdala neuroadaptation to acute withdrawal from a palatable diet. These findings contribute to the comprehension of the mechanisms that link early life events and altered feeding behavior and related morbidities such as obesity in adulthood. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.International Journal of Developmental Neuroscience 11/2014; 40. DOI:10.1016/j.ijdevneu.2014.11.003 · 2.92 Impact Factor