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Background The neurotransmitter dopamine ( DA), acting in various mesolimbic brain regions, is well known for its role in promoting motivated behaviors, including ethanol (EtOH) drinking. Indirect evidence, however, suggests that DA in the perifornical lateral hypothalamus ( PF/ LH) has differential effects on EtOH consumption, depending on whether it acts on the DA 1 ( D1) or DA 2 ( D2) receptor subtype, and that these effects are mediated in part by local peptide systems, such as orexin/hypocretin ( OX) and melanin-concentrating hormone ( MCH), known to stimulate the consumption of EtOH. Methods The present study in brain-cannulated Sprague- Dawley rats measured the effects of dopaminergic compounds in the PF/ LH on drinking behavior in animals trained to consume 7% EtOH and also on local peptide mRNA expression using digoxigenin-labeled in situ hybridization in EtOH-naïve animals. Results Experiments 1 and 2 showed that the D1 agonist SKF81297 (10.8 nmol/side) in the PF/ LH significantly increased food intake, while tending to increase EtOH intake, and the D1 antagonist SCH23390 significantly decreased EtOH intake without affecting food intake. In contrast, the D2 agonist quinelorane (6.2 nmol/side) in the PF/ LH significantly reduced EtOH consumption, while the D2 antagonist sulpiride increased it. Experiments 3 and 4 revealed differential effects of PF/ LH injection of the DA agonists on local OX mRNA, which was increased by the D1 agonist and decreased by the D2 agonist. These DA agonists had no impact on MCH expression. Conclusions These results support a stimulatory role of the PF/ LH D1 receptor in promoting the consumption of both EtOH and food, in contrast to a suppressive effect of the D2 receptor on EtOH drinking. They further suggest that these receptors affect consumption, in part, through local OX-expressing neurons. These findings provide new evidence for the function of PF/ LH DA receptor subtypes in controlling EtOH and food intake. [ABSTRACT FROM AUTHOR]

Background Glutamate ( GLUT) in the lateral hypothalamus ( LH) has been suggested to mediate reward behaviors and may promote the ingestion of drugs of abuse. This study tested the hypothesis that GLUT in the LH stimulates consumption of ethanol ( EtOH) and that this effect occurs, in part, via its interaction with local peptides, hypocretin/orexin ( OX), and melanin-concentrating hormone ( MCH). Methods In Experiments 1 and 2, male Sprague- Dawley rats, after being trained to drink 9% EtOH, were microinjected in the LH with N-methyl- d-aspartate ( NMDA) or its antagonist, D- AP5, or with alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid ( AMPA) or its antagonist, CNQX-ds. Consumption of EtOH, chow, and water was then measured. To provide an anatomical control, a separate set of rats was injected 2 mm dorsal to the LH. In Experiment 3, the effect of LH injection of NMDA and AMPA on the expression of OX and MCH was measured using radiolabeled in situ hybridization ( ISH) and also using digoxigenin-labeled ISH, to distinguish effects on OX and MCH cells in the LH and the nearby perifornical area ( PF) and zona incerta ( ZI). Results When injected into the LH, NMDA and AMPA both significantly increased EtOH intake while having no effect on chow or water intake. The GLUT receptor antagonists had the opposite effect, significantly reducing EtOH consumption. No effects were observed with injections 2 mm dorsal to the LH. In addition to these behavioral effects, LH injection of NMDA significantly stimulated expression of OX in both the LH and PF while reducing MCH in the ZI, whereas AMPA increased OX only in the LH and had no effect on MCH. Conclusions Glutamatergic inputs to the LH, acting through NMDA and AMPA receptors, appear to have a stimulatory effect on EtOH consumption, mediated in part by increased OX in LH and PF and reduced MCH in ZI. [ABSTRACT FROM AUTHOR]

Background: Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods: Sprague–Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the μ-receptor agonist [d-Ala2, N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO), δ-receptor agonistd-Ala-Gly-Phe-Met-NH2 (DALA), or κ-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results: A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the δ-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the κ-agonist U-50,488H, which decreased ethanol intake, and the μ-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions: The δ-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the κ-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the δ- and κ-receptors, respectively. These results suggest that enkephalin via the δ-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the κ-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle. [ABSTRACT FROM AUTHOR]

Objective: Given the frequency of transition from anorexia nervosa to bulimia nervosa, this study investigated whether a history of activity-based anorexia (ABA) during adolescence would promote binge eating during adulthood in female rats. Method: Adolescent rats were given 1-h unlimited access to chow and ad libitum access to a running wheel until body weight reached <80%, indicating the development of ABA. During adulthood, all groups were given 21 days of access to a palatable food for 2 h/day and ad libitum access to chow. Results: During adolescence, rats in the ABA paradigm developed increased wheel running and decreased food intake, reaching <80% of body weight after 3 days. However, there were no significant differences between groups in the amount of binge food consumed during adulthood. Conclusion: A brief episode of ABA during adolescence did not lead to increased binge eating later in life. Longer-term models are needed to determine whether a propensity toward binge eating may result from more sustained ABA during adolescence. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated whether restricted access to a highly palatable combination of sugar and fat, without food deprivation, would instigate binge eating and increase body weight. Findings showed that the body weight of rats increased due to large meals and decreased between binges as a result of self-restricted intake of chow following binges. They suggest an animal model of binge eating in which nonfood-deprived rats binge on a sugar and fat rich food.

Objective: Activity-based anorexia is an animal model of anorexia nervosa in which limited access to standard lab chow combined with voluntary wheel running leads to hypophagia and severe weight loss. This study tested whether activity-based anorexia could be prevented or reversed with palatable foods. Method: Male rats were divided into sedentary or ad libitum-running groups and maintained on 1 h daily access to standard chow plus one of the following: sugar, saccharin, vegetable fat (shortening), or sweet high-fat chow. Results: Access to the sweet high-fat chow both reversed and prevented the weight loss typical of activity-based anorexia. Vegetable fat attenuated body weight loss, but to a lesser degree than the sweet high-fat diet. The addition of saccharin or sucrose solutions to the standard lab-chow diet had no effect. Conclusion: The results suggest that certain palatable diets may affect the development of, and recovery from, activity-based anorexia. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [ABSTRACT FROM AUTHOR]

Background: The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. Methods: Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. Results: In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. Conclusions: In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse. [ABSTRACT FROM AUTHOR]

Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN). Method: Adult, male Sprague–Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured. Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN. Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol. [ABSTRACT FROM AUTHOR]

Background: The neuropeptide galanin increases food intake. Chronic ethanol (EtOH) increases the expression of galanin in the hypothalamus. The research presented here examines the effects of microinjection of galanin in the third ventricle on voluntary alcohol intake. Methods: Male Sprague Dawley rats with a cannula in the third ventricle were given access to increasing concentrations of EtOH for 12 hr/day until all acquired a preference for 7% EtOH over water in a two-bottle choice. Rats then received a microinjection of galanin (0, 1, and 3 nmol) alone or in combination with the galanin antagonist M40 (1 nmol) and with M40 alone to determine the effects on EtOH and water intake. Tests were conducted during both the light and dark periods of a 12:12-hr light-dark cycle with food available ad libitum. As a control for galanin-induced calorie intake, both EtOH and food were measured in a subset of rats during the dark. Results: Microinjections of galanin (1.0 and 3.0 nmol) increased EtOH consumption during both periods of the light-dark cycle. Galanin's effect on ethanol intake during the light was large relative to the very low intake of food and water during this period. Rats increased their intake of EtOH but not food. Receptor specificity for galanin (3 nmol) was shown by the galanin antagonist M40, which blocked the increase in EtOH intake. M40 alone decreased EtOH intake slightly. Conclusions: These data show that galanin injected in the third ventricle increases EtOH consumption and that the effect can occur during both the light and the dark periods of the diurnal cycle in the presence of food and water. This suggests that galanin may play a role in augmenting voluntary alcohol intake and perhaps the development of alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: Recent evidence has demonstrated that ethanol intake can stimulate the expression and production of the feeding-stimulatory peptide, galanin (GAL), in the hypothalamic paraventricular nucleus (PVN), and that PVN injection of this peptide, in turn, can increase the consumption of ethanol. To test the hypothesis that other feeding-related systems are involved in ethanol intake, this study examined the effect of ethanol on the hypothalamic opioid peptides, enkephalin (ENK), and dynorphin (DYN)., Method: Adult, male Sprague-Dawley rats were trained to voluntarily drink increasing concentrations of ethanol, up to 9% v/v, on a 12-hour access schedule or were given a single injection of ethanol (10% v/v) versus saline vehicle. The effect of ethanol on GAL, ENK, and DYN mRNA was measured using real-time quantitative polymerase chain reaction and radiolabeled in situ hybridization, while radioimmunoassay was used to measure peptide levels. In addition to blood alcohol, circulating levels of triglycerides (TG), leptin, and insulin were also measured., Results: The data demonstrated that: (1) rats voluntarily drinking 9% v/v ethanol (approximately 2.0 g/kg/d) show a significant increase in GAL, ENK, and DYN mRNA in the PVN compared with water-drinking rats; (2) voluntary consumption of ethanol also increases peptide levels of ENK and DYN in the PVN; (3) acute injection of 10% ethanol (1.0 g/kg of 10% v/v) similarly increases the expression of GAL, ENK, and DYN in the PVN; and (4) ethanol consumption and injection, while having little effect on leptin and insulin, consistently increase circulating levels of TG as well as alcohol, both of which are strongly, positively correlated with peptide expression in the PVN., Conclusions: These findings, together with published studies, suggest a possible role for hypothalamic opioid peptides in the drinking of ethanol. Based on evidence that dietary fat and lipid injections stimulate the PVN peptides and injection of the opiates and GAL increase ethanol intake, it is proposed that both TG and alcohol in the circulation, which are elevated by the ingestion or injection of ethanol, are involved in stimulating these peptides in the PVN, which in turn promote further consumption of ethanol.