Search

The present study aimed to examine the mediatory role of the dopaminergic system in the food intake induced by intracerebroventricular (ICV) injection of glycine in neonatal 3-h feed-deprived (FD3) meat-type chickens. In the first and second experiments, birds were ICV injected using low and high doses of glycine (50, 100 and 200 nmol) and strychnine (50, 100 and 200 nmol), respectively. In experiments 3-9, the behaviorally subeffective doses of dopamine (10 nmol), 6-OHDA (2.5 nmol), SCH 23,390 (D1 antagonist; 5 nmol), AMI-193 (D2 antagonist; 5 nmol), NGB2904 (D3 antagonist; 6.4 nmol) and L-741,742 (D4 antagonist; 6 nmol) were, respectively, co-administrated with glycine (200 nmol) in FD3 5-day-old chicks to investigate possible interplay of dopamine receptors in glycine-induced feeding behavior. Then, cumulative food intake based on body weight percentage (%BW) was determined at 30, 60 and 120 min after the injection. According to the results, dopamine significantly boosted the hypophagia induced by glycine at all-time intervals (p ≤ 0.001). These results combined with the previous findings suggest an interplay between dopamine and glycine in chicken's brain in which D1 receptor-mediated food intake induced by glycine.

RFamide-related Peptide-3(RFRP-3) plays a key role in appetite regulation. The current study aimed to determine the effect of RFRP-3(Neuropeptide VF) on feeding behavior and its interaction with the melanocortin and corticotropin systems on food intake in the neonatal broiler-type chickens. In experiments 1 and 2, chickens received intracerebroventricular (ICV) injection of control solution besides RFRP-3 (4, 8, and 16 nmol) and RF9 (NPFF receptors antagonist; 4, 8 and 16 nmol) respectively to investigate the effective doses of RFRP-3 and RF9. Experiments 3–8 have been designed to investigate the mediatory role of CRF1/CRF2 and MC3R/MC4R on food intake induced by RFRP-3 in chickens. Finally, in experiments 8–11, the synergistic effect between the MC3R and MC4R with RFRP-3 have been investigated via ICV co-injection of sub-effective doses of RFRP-3 + γ1-MSH and PG-931. Then, cumulative food intake was recorded at 30, 60, and 120 min after injection. According to the results, co-injection of astressin-B and RFRP-3, significantly attenuated hypophagic effect of RFRP-3; while astressin2-B reversed this effect of RFRP-3 (p

Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMCARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DAVTA neurons). We further revealed that POMCARH neurons project to the VTA and provide an inhibitory tone to DAVTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMCARH→VTA circuit in mice increases body weight and food intake, and reduces depression-like behaviors and anhedonia in mice exposed to chronic restraint stress. Thus, our results identified a novel neurocircuitry regulating feeding and mood in response to stress.

The effect of spineless cactus intake (Opuntia ficus-indica) on blood glucose (BG) levels in lactating sows and its impact on daily and total feed intake (dFI−1 and TFI, respectively), body weight loss (BWL), and weaning-estrus interval length (WEI) were evaluated. Thirty-four hybrid (Yorkshire × Landrace × Pietrain) sows in lactation phase were used. Sows were divided into two groups: G1 (n = 17) where they received commercial feed and G2 (n = 17) provided with commercial feed plus an average of 2.0 ± 0.5 kg spineless cactus, based on a sow’s body weight. The variables evaluated were BG, dFI−1, TFI, BWL, and WEI. Statistical analysis was performed by using a fixed and mixed model methodology, under a repeated measurements experiment. Group effects were found on all analyzed variables (P

Central regulatory mechanisms for food intake regulation vary among animals. Evidence from animal studies suggests central opioids and dopamine have prominent role on appetite regulation but their interaction(s) have not been studied in layer-type chicken. Thus, in this study six experiments designed to investigate intracerebroventricular (ICV) administration of SCH23390 (D1 like receptors antagonist), Sulpride (D2 like receptors antagonist), DAMGO (μ-opioid receptors agonist), DPDPE (δ-opioid receptors agonist), U-50488H (κ-opioid receptors agonist) on feeding behavior in 3 h food deprived neonatal layer-type chickens. In experiment 1, chicks ICV injected with control solution, SCH23390 (2.5 nmol), DAMGO (125 pmol) and their combination (SCH23390 + DAMGO). In experiment 2: control solution, SCH23390 (2.5 nmol), DPDPE (δ-opioid receptors agonist, 40 pmol) and SCH23390 + DPDPE were applied to the birds. In experiment 3, injections were control solution, SCH23390 (2.5 nmol), U-50488H (30 nmol) and SCH23390 + U-50488H. In experiments 4–6 were similar to experiments 1–3 except Sulpride (2.5 nmol) applied instead of SCH23390. Then, cumulative food intake was recorded until 120 min after injection. According to the results, ICV injection of DAMGO (125 pmol) significantly decreased food intake but co-injection of DAMGO + SCH23390 diminished DAMGO-induced hypophagia (P 0.05). Furthermore, Sulpride had no role on DAMGO, DPDPE and U-50488H-induced food intake (P > 0.05). These results suggest there is an interaction between opioidergic and dopaminergic systems via μ and D1 receptors in appetite regulation in chicken.

Rationale Synergistic or supra-additive interactions between the anorectics (dex)fenfluramine and phentermine have been reported previously in the rat and in the clinic. Studies with 5-HT2C antagonists and 5-HT2C knockouts have demonstrated dexfenfluramine hypophagia in the rodent to be mediated by actions at the 5-HT2C receptor. Given the recent FDA approval of the selective 5-HT2C agonist lorcaserin (BELVIQ®) for weight management, we investigated the interaction between phentermine and 5-HT2C agonists on food intake. Objectives This study aims to confirm dexfenfluramine-phentermine (dex-phen) synergy in a rat food intake assay, to extend these findings to other 5-HT2C agonists, and to determine whether pharmacokinetic interactions could explain synergistic findings with particular drug combinations. Methods Isobolographic analyses were performed in which phentermine was paired with either dexfenfluramine, the 5-HT2C agonist AR630, or the 5-HT2C agonist lorcaserin, and inhibition of food intake measured in the rat. Subsequent studies assessed these same phentermine-drug pair combinations spanning both the full effect range and a range of fixed ratio drug combinations. Satellite groups received single doses of each drug either alone or in combination with phentermine, and free brain concentrations were measured. Results Dex-phen synergy was confirmed in the rat and extended to the 5-HT2C agonist AR630. In contrast, although some synergistic interactions between lorcaserin and phentermine were observed, these combinations were largely additive. Synergistic interactions between phentermine and dexfenfluramine or AR630 were accompanied by combination-induced increases in brain levels of phentermine. Conclusions Dex-phen synergy in the rat is caused by a pharmacokinetic interaction, resulting in increased central concentrations of phentermine.

The purpose of this study was to examine the effects of intracerebroventricular injection of metoprolol (a β1 adrenergic receptor antagonist), ICI 118,551 (a β2 adrenergic receptor antagonist), and SR 59230R (a β3 adrenergic receptor antagonist) on ghrelin-induced food and water intake by 3-h food-deprived (FD3) cockerels. The chickens were randomly allocated to 4 treatment groups with 8 replicates in each group. A cannula was surgically implanted into the lateral ventricle of the brain. In experiment 1, chickens received the β1 adrenergic receptor antagonist (24 nmol) before injection of the ghrelin (0.6 nmol). In experiment 2, chickens received the β2 adrenergic receptor antagonist (5 nmol) before injection of the ghrelin (0.6 nmol). In experiment 3, birds were injected with ghrelin (0.6 nmol) after the β3 adrenergic receptor antagonist (20 nmol). Cumulative food and water intake were recorded 3-h post injection and analyzed by two-way analysis of variance. According to the results, ghrelin injection reduced food and water intake by broiler cockerels (p ≤ 0.05). The effect of ghrelin on food intake was significantly attenuated by pretreatment with the β2 receptor antagonist (p ≤ 0.05). Furthermore, the β2 receptor antagonist had no effect on water intake induced by ghrelin. Also, pretreatment with the β1 and β3 receptors antagonists had no effect on ghrelin-induced food and water intake. These results suggest that the effect of ghrelin on cumulative food intake by cockerels is mediated via β2 adrenergic receptors.

Clinical literature demonstrates that nearly all atypical antipsychotic drugs (AAPDs) are associated with weight gain. The magnitude of weight gain, however, varies between doses of drugs and exposure period as well as in different age groups. Data on AAPDs like quetiapine (QUE), risperidone and weight gain have been found variable in clinical and preclinical trials. The metabolic safety of these drugs in pregnant women has not been thoroughly investigated so far. Therefore, present study is designed to investigate the effect of gestational exposure to equivalent therapeutic doses of AAPDs, QUE and RISP on weight gain in female pregnant rats. The results indicate that there was mild reduction in body weight gain and food consumption in RISP exposed rats. Similarly, mild weight loss was also observed in QUE exposed dams inspite of significant drug induced anorexia/hypophagia. These drugs were found either neutral in weight gain or may induce mild weight loss in female adult rats. This study also demonstrates that multifunctional mechanisms might be involved for alteration in feeding pattern and body weight gain.

In mammals, LPS regulate feeding primarily through the 5-HT(1A) and 5-HT(2c) receptors within the brain. However, the central effect of 5-HT(1A) and 5-HT(2c) on LPS-induced feeding behavior has not been studied in non-mammalian species. Also, the role of glutamatergic system in LPS-induced anorexia has never been examined in either mammalian or non-mammalian species. Therefore, in this study, we examined the role of serotonergic and glutamatergic systems on LPS-induced anorexia in chickens. Food intake was measured in chickens after centrally administered lipopolysaccharide (LPS) (20 ng) (0 h), followed by intracerebroventricular (ICV) injection of the 5-HT(1A) autoreceptor agonist (8-OH-DPAT, 61 nmol), 5-HT(2c) receptor antagonist (SB 242084, 30 nm), and NMDA receptor antagonist (DL-AP5, 5 nm) at the onset of anorexia (4 h). In the following experiments, we used DL-AP5 before 5-HT (10 μg) and SB242084 before glutamate (300 nm) for evaluation of the interaction between 5-HTergic and glutamatergic systems on food intake. The results of this study showed that SB 242084 and DL-AP5 significantly attenuated food intake reduction caused by LPS (P 0.05) but 8-OH-DPAT had no effect. In addition, 5-HT-induced anorexia was significantly attenuated by DL-AP5 pretreatment (P 0.05), while SB 242084 had no effect on glutamate-induced hypophagia. These results indicated that 5-HT and glutamate (via 5-HT(2c) and NMDA receptor, respectively) dependently regulate LPS-induced hypophagia in chickens.

AT(1)-blockade has been shown to induce weight loss in animals or patients. The aim of this study was to investigate whether weight reduction after AT(1)-blockade is dependent on dose, blood pressure reduction and leptin signalling. Spontaneously hypertensive rats (SHR) and lean and obese Zucker rats were treated for 4 weeks with candesartan (0, 2, 6 or 16 mg/kg/day). Body weight, food intake and hypothalamic mRNA levels of (an)orexigenic peptides were determined. Obese Zucker rats served as a model of primary leptin resistance. In SHR, body mass index and food intake were decreased selectively by 16 mg/kg/day candesartan but not after using normal (2 mg/kg/day) or supranormal (6 mg/kg/day) doses. Correlation analysis between blood pressure and body weight indicated no relationship of hypotensive potency on weight loss. The hypothalamic mRNA levels of the orexigenic peptide MCH (melanin-concentrating hormone) were diminished in parallel. Consistent to the results in SHRs, 16 mg/kg/day candesartan revealed a decrease of body weight, food intake and hypothalamic MCH mRNA levels in lean Zucker rats. In obese Zucker rats, none of these parameters were reduced by candesartan. Loss of body weight and hypophagia are not general features of AT(1)-blockers, since neither was seen after normal or moderately supranormal doses, but they were, after the highest doses. These actions of AT(1)-blockers occur independently of their ability to lower blood pressure. They do depend on an intact leptin signalling, since they were absent in obese Zucker rats that feature a genetic mutation of the leptin receptor.

Neuropeptide Y (NPY) is implicated in the pathophysiology of affective illness. Multiple receptor subtypes (Y1R, Y2R, and Y5R) have been suggested to contribute to NPY’s effects on rodent anxiety and depression-related behaviors. To further elucidate the role of Y1R in (1) NPY’s anxiolytic-like effects and (2) fluoxetine’s antidepressant-like and neurogenesis-inducing effects. Mice lacking Y1R were assessed for spontaneous anxiety-like behavior (open field, elevated plus-maze, and light/dark exploration test) and Pavlovian fear conditioning, and for the anxiolytic-like effects of intracerebroventricularly (icv)-administrated NPY (elevated plus-maze). Next, Y1R −/− were assessed for the antidepressant-like effects of acute fluoxetine in the forced swim test and chronic fluoxetine in the novelty-induced hypophagia test, as well as for chronic fluoxetine-induced hippocampal neurogenesis. Y1R −/− exhibited largely normal baseline behavior as compared to +/+ littermate controls. Intraventricular administration of NPY in Y1R −/− mice failed to produce the normal anxiolytic-like effect in the elevated plus-maze test seen in +/+ mice. Y1R mutant mice showed higher immobility in the forced swim test and longer latencies in the novelty-induced hypophagia test. In addition, Y1R −/− mice responded normally to the acute and chronic effects of fluoxetine treatment in the forced swim test and the novelty-induced hypophagia test, respectively, as well as increased neuronal precursor cell proliferation in the hippocampus. These data demonstrate that Y1R is necessary for the anxiolytic-like effects of icv NPY, but not for the antidepressant-like or neurogenesis-inducing effects of fluoxetine. The present study supports targeting Y1R as a novel therapeutic target for anxiety disorders.

Rationale. 5-HT1B receptors are thought to be one of the receptor subtypes that mediate the inhibitory control of serotonin on food intake and satiety. Objective. To use the selective 5-HT1B receptor agonist, CP-94,253 as a probe of 5-HT1B receptor function in feeding behaviour, and to confirm the pharmacological selectivity of CP-94,253-induced hypophagia with a range of antagonists. Methods. Dose-response functions for CP-94,253 (0, 1.25, 2.5, 5.0 mg/kg; IP) were determined in animals consuming wet mash in a 40-min test session during which time-sampled behavioural observations were collected to evaluate satiety sequences. A meal patterning study was carried out in a separate group of rats. The 5-HT1A antagonist WAY 100,635 (0, 1.0, 3.0 mg/kg; SC), the 5-HT1B/1D antagonist GR 127,935 (0, 3 mg/kg; IP), and the 5-HT1B antagonist SB 224289 (0, 2.5, 5.0 mg/kg; IP) were used to confirm that 5-HT1B receptor subtypes were responsible for the action of CP-94,253 on feeding behaviour. Results. CP-94,253 (2.5 mg/kg) reduced food intake and preserved the satiety sequence in animals consuming a diet of mash. GR 127,935 (3.0 mg/kg) and SB 224289 (2.5 mg/kg), but not WAY 100,635, attenuated the hypophagic effect of the 5-HT1B agonist, and returned the changes in satiety sequence to control patterns. Meal patterning analyses indicated that CP-94,253 (2.5 mg/kg) reduced food intake through a decrease in meal size and duration in the absence of any alteration in the rate of eating. A hypodipsic action of CP-94,253 was also observed (2.5 and 5.0 mg/kg). Conclusion. These findings imply that 5-HT1B receptors regulate discrete elements of satiety. We discuss the potential role of 5-HT1B agonists for the treatment of obesity.

Rationale: Activation of 5-HT2C receptors is thought to enhance satiety and to mediate the action of the prototypical anorectic drug d-fenfluramine. Objective: Four experiments investigated the role of the 5-HT2C receptor in the modulation of feeding by comparison of the effects of the putative selective 5-HT2C receptor agonist Ro 60-0175 and d-fenfluramine on feeding behaviour. Methods: Microstructural analyses of meal patterning and drinking of a palatable solution were made over a range of drug doses administered to male Lister hooded rats. Results: Ro 60-0175 increased the latency to the first meal (3 mg/kg) and reduced meal size (1 mg/kg). d-Fenfluramine (1 mg/kg) produced a similar behavioural pattern, but 3 mg/kg produced a more profound hypophagia that persisted for 10–12 h. Ro 60-0175 (1, 3 mg/kg) and d-fenfluramine (1. 5 mg/kg) reduced ingestion of a palatable glucose/saccharin solution, by a reduction in the number of bouts of licking, with little effect on the size of individual bouts. d-Fenfluramine-induced hypophagia (2.1 mg/kg) was challenged by the administration of the selective 5-HT2C receptor antagonist SB 242084 (1, 3 mg/kg) in the meal patterning paradigm. SB 242084 significantly attenuated the decrease in feeding rate and increase in latency to feed produced by d-fenfluramine, but had no effect on the fenfluramine-induced reduction in meal size. A similar pattern of results was obtained when Ro 60-0175-induced hypophagia (3 mg/kg) was challenged by SB 242084 (1, 3 mg/kg). Conclusions: These results demonstrate that Ro 60-0175 is a useful probe of the importance of 5-HT2C activation in the control of food intake and support the hypothesis that activation of 5-HT2C receptors is a critical aspect of the hypophagic action of d-fenfluramine. The 5-HT2C receptor may prove to be a useful target in the development of clinically effective drugs for the treatment of obesity.

Several investigators have reported a drop in oxygen (O2) consumption (VO2) and body temperature in laboratory animals during normobaric or hypobaric hypoxia. Hypophagia, with normal efficiency of protein utilisation for growth, was also observed. It has recently also been observed that hypometabolism is present during anaemic hypoxia. The present study was designed to test the experimental hypothesis that anaemic hypoxia induces hypometabolism secondary to hypophagia. Episodes of anaemia were created in adult male rats by either blood withdrawal through cardiac puncture (haemorrhagic anaemia) or phenylhydrazine administration (haemolytic anaemia). Haematrocrit, VO2, and food consumption, as indirect estimations of the level of anaemia, energy production, and appetite, respectively, were serially measured in all animals during 7 days (acute experiments) or 17 days (chronic experiments). Positive correlations were found between the three parameters during development of and recovery from anaemia during each anaemic episode. When the amount of food offered to non-anaemic rats was equalised to that freely eaten by anaemic rats, VO2 dropped in the former to almost the level found in the latter. Body composition changed during chronic anaemia because of a decrease in the lipid fraction of the body. The results confirmed the working hypothesis that hypometabolism, which has been considered as an immediate, emergency-type response to both hypoxic and anaemic hypoxia, can be considered as a response secondary to hypophagia because of depressed appetite. How appetite is adapted to the mechanisms which control O2 convection and O2 availability is not known at present.

Tolerance to amphetamine-induced hypophagia is lost when drug injections are withdrawn for 4 weeks while milk tests are continued (Wolgin and Hughes 1996). The purpose of this study was to determine whether the loss of tolerance is a function of drug withdrawal per se. Rats made tolerant to amphetamine (2 mg/kg, IP) were assigned to one of three groups. During the next 4 weeks (phase), one group continued to receive amphetamine injections prior to daily milk tests (Before group), one group received drug injections after the milk tests (After group), and one group received injections of saline prior to the milk tests (Saline group). Dose-response tests revealed that the Before group retained tolerance, whereas the After and Saline groups lost tolerance. When retested with chronic injections of amphetamine prior to milk, the After and Saline groups reacquired tolerance more rapidly, and to a greater extent, than non-tolerant controls. These results demonstrate that the loss of tolerance is not due to drug withdrawal per se, but may be due to the unlearning of behavioral strategies previously acquired under the drug.

The purpose of this study was to determine whether prior sensitization of stereotypy interferes with the development and retention of tolerance to amphetamine-induced hypophagia. Rats were given intermittent injections of either amphetamine (2.5 mg/kg) to induce sensitization of stereotypy, or saline. Subgroups from each group then received daily injections of either amphetamine (2 mg/kg) or saline and access to milk for 30 min. Both sensitized and nonsensitized groups became tolerant to drug-induced hypophagia at about the same rate and to about the same extent. Such tolerance was accompanied by a decrease in the frequency of stereotyped movements while milk was available. The rats were then given daily milk tests for 4 weeks without injections. Subsequent tests with amphetamine revealed that both groups lost tolerance to drug-induced hypophagia and displayed more intense stereotypy than they had prior to drug withdrawal. We conclude that sensitization of stereotypy produced by intermittent injections of amphetamine (2.5 mg/kg) does not retard the development of tolerance to drug-induced hypophagia and does not alter the rat's ability to suppress stereotyped movements. However, the loss of tolerance following drug withdrawal may have been due to the development of more intense stereotypy and/or the "unlearning" of previously acquired strategies for suppressing stereotypy.

During a long-term (7-day) continuous exposure of rats to β-endorphin from an implanted minipump by the subcutaneous route, changes in their motor activity (stereotypy) and pain sensitivity (hypoalgesia) were similar, though less marked, than those observed during such exposure by the intracerebral route, whereas the change in feeding behavior with the subcutaneous (peripheral) route of β-endorphin administration (hyperphagia) was opposite to that seen with intracerebral administration (hypophagia).

Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3-chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H-indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition.

We explored the effects of O,O,S-trimethyl phosphorothioate (OOS-TMP) on body temperatures in Fischer 344 female rats. The 7-day LD50 p.o. for Fischer 344 female rats was found to be 11.8 mg/kg. OOS-TMP induced long-lasting (more than 48 h) and extensive hypothermia at dosesor = 14 mg/kg at a typical laboratory temperature (22 degrees C) while it produced typical symptoms at 10 mg/kg without hypothermia. In contrast, pair-fed (to 20 mg/kg rats) rats (n = 4) did not become hypothermic, negating any role of hypophagia in OOS-TMP associated hypothermia. We next investigated the effects of housing temperatures on toxicities at a LD50 dose (12 mg/kg). At 30 degrees C (n = 11) and 22 degrees C (n = 13), rats did not have hypothermic bouts but at 15 degrees C, eight out of ten rats had. Evidence that changes of housing temperatures neither modified clinical symptoms nor changed mortality rates discards a possibility of hypothermia being involved in delayed toxicity. A novel result of the present study suggests that thermoregulation may be heavily impaired by a special class of organophosphorus compounds.

The purpose of this study was to determine the effect of manipulating the interdose interval (IDI) on the suppression of milk intake induced by haloperidol (HAL). Groups of rats were given chronic injections of either HAL (0.625 mg/kg) or saline at IDIs of 1, 2, 7, or 14 days. Dose-response curves were determined at the conclusion of the chronic phase. The results indicated that injections of HAL given at IDIs of 1 or 2 days produced neither tolerance nor sensitization, whereas injections given at intervals of 7 or 14 days produced sensitization. Sensitization was also observed in the control groups, perhaps as a result of the intermittent schedule of HAL injections given during the dose-response tests. Sensitization to HAL was not accompanied by changes in sensitivity to amphetamine. The results of this experiment are consistent with those of other studies in showing that the behavioral effects of neuroleptics are strongly influenced by the schedule of injections. In addition, evidence is presented that sensitization to HAL-induced hypophagia is contingent on behavioral experience under the drug.

Anorexia nervosa is a clinically significant illness that may be associated with permanent medical complications involving almost every organ system. The paper raises a question whether some of them are associated with premorbid vulnerability such as subcellular ion channel abnormalities ('channelopathy') that determines the clinical expression of the bodily response to self-imposed malnutrition. Aberrant channels emerge as a tempting, if rather speculative alternative to the notion of cognitively-driven neurotransmitter modulation deficit in anorexia nervosa. The concept of channelopathies is in keeping with some characteristics of anorexia nervosa, such as a genetically-based predisposition to hypophagia, early onset, cardiac abnormalities, an appetite-enhancing efficacy of some antiepileptic drugs, and others. The purpose of this article is to stimulate further basic research of ion channel biophysics in relation to restrictive anorexia.

Administration of a single low dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has been demonstrated to elicit long-lasting antidepressant effects in humans with depression, as well as in rodent models of depression. Although pharmacological studies have implicated the GluN2B subunit of the NMDA receptor in these effects, drugs targeting this subunit have off-target actions, and systemic administration of these compounds does not allow for delineation of specific brain regions involved. In this study, we assessed the role of GluN2B in the bed nucleus of the stria terminalis (BNST) in novelty-induced hypophagia (NIH) in mice. First, we verified that ketamine, as well as the GluN2B antagonist Ro25–6981, decreased the latency to consume food in a novel environment in a version of the NIH test. We then hypothesized that GluN2B-containing receptors within the BNST may be a target of systemic ketamine and contribute to behavioral effects. Through the combination of a GluN2B-floxed mouse line and stereotaxic delivery of lentiviral Cre recombinase, we found that targeted knockdown of this subunit within the BNST mimicked the reduction in affective behavior observed with systemic ketamine or Ro25–6981 in the NIH test. These data suggest a role for GluN2B-containing NMDARs within the BNST in the affective effects of systemic ketamine.

Precise electrolytic lesions were placed in the dorsomedial (DMNL) and ventromedial (VMNL) hypothalamic nuclei of weanling rats to study the effect on food and water intake, body weight and length and body composition. Lesions in the DMN consistently resulted in hypophagia, hypodipsia and decreased ponderal and linear growth, both when compared with VMNL rats and with sham-operated controls. The DMNL rats contained more carcass water and lean body mass but less fat than the VMNL rats. The lesion effect persisted in the DMNL rats even after placement of minute lesions of 2.5 mC, while such lesions failed to elicit the changes found with larger lesions in the VMNL rats. The data show that the DMN, at least in the weanling rat, appear to be part of the “feeding center” and water intake circuitry. They also show the minuteness of the area involved and its sharp functional and anatomical delineation from the VMN.

Electrolytic bilateral lesions of the dorsomedial hypothalamic nucleus of both female and male mature rats resulted in hypophagia, hypodipsia and decreased spontaneous running activity. The latter is not associated with increased fat deposition. Resting oxygen consumption was reduced in both sexes, but significantly only in the males. Thyroid weight was normal in both sexes but ovaries and adrenals were lighter in the females and the pituitary was lighter in the male rats with lesions. The data show that the dorsomedial hypothalamic nucleus is involved in hypothalamic mechanisms controlling food intake, water intake and spontaneous activity not only in the weanling rat as previously demonstrated, but in the mature rat as well.

The 5-HT1B agonist RU24969 when given either systemically (1 mg/kg SC) or by infusion (0.5, 1.0, 2.0 micrograms) into the region of the paraventricular nucleus of the hypothalamus caused dose-dependent hypophagia in rats previously deprived of food for 18 h. Similar results were obtained at the above dosages of 1-[3-(trifluoromethyl) phenyl] piperazine (TFMPP), which acts on 5-HT1B and possibly also on 5-HT1C receptors. Neither drug significantly affected locomotion following central administration. Food intake was significantly decreased when the 5-HT1A agonist 8-OH-DPAT was given systemically (1 mg/kg SC) to rats previously deprived of food but was unaffected when 8-OH-DPAT (1 microgram) was infused into the paraventricular nucleus of both food-deprived and free feeding rats. Therefore, hypophagia occurs when hypothalamic 5-HT1B (and possibly 5-HT1C) but not 5-HT1A receptors are activated.

Anatomical studies have identified a network of structures at several levels of the avian brain whose location and connections suggest that they are involved in the neural control of feeding in the pigeon. The network originates in a cranial nerve sensory nucleus innervating the oral region and includes striatal and limbic components. Bilateral lesions placed in several of the structures of this network produced disturbances of feeding and drinking, including aphagia, adipsia, and hypophagia. It is suggested that further neurobehavioral analysis of these structures may clarify the role of extrahypothalamic mechanisms in the neural control of feeding.

A series of rats were lesioned unilaterally through hypothalamic electrodes from which drinking and self-stimulation could be elicited. The lesions abolished electrically-induced drinking and severely reduced rates of self-stimulation. In addition, a transient adipsia and hypophagia resulted from lesioning in several of the animals.