Food Intake In Food-deprived Rats Research Articles

Contextual fear cues inhibit eating in food-deprived male and female rats

Previously we have shown that food-deprived male and female rats inhibit food consumption when presented with a discrete conditioned stimulus that signals danger. Here, in a series of three experiments, we examined whether contextual conditioned stimuli can exert the same effect. Experiment 1 paired a distinct context with footshocks, to examine food intake in food-deprived rats upon re-exposure to the context. Experiment 2 used a discrimination protocol with two alternating contexts; rats were given food in one, and received footshocks in the other. This protocol allowed us to monitor food consumption during training in a context never associated with footshocks, and to evaluate consumption at test in a context that had been previously paired with footshocks. Experiments 1 and 2 compared experimental groups to controls that never received footshocks. Experiment 3 used a within-subjects design to assess the specificity of the inhibition by the contextual cues, separate from any generalized effects due solely to the prior experience of footshocks. Our results demonstrate that similar to discrete cues, contextual cues previously associated with aversive events can inhibit feeding in food-deprived animals. These findings are important for our understanding of environmental contributions to the control of food intake.

Eating caused by neuropeptide-Y injection in the paraventricular hypothalamus: response to (+)-fenfluramine and (+)-amphetamine in rats

(+)-Fenfluramine and (+)-amphetamine have been compared for their ability to reduce food intake in food-deprived rats or eating caused by injecting neuropeptide-Y in the paraventricular hypothalamus of free feeding rats. (+)-Fenfluramine at doses ranging from 0.625 to 5 mg kg-1 reduced eating caused by neuropeptide-Y more effectively than it did the food intake of food-deprived rats, whereas (+)-amphetamine (dose range 0.625-2.5 mg kg-1) reduced both types of eating to a similar extent. The results confirm that (+)-fenfluramine, although less potent than (+)-amphetamine in reducing eating by food-deprived rats, markedly reduces overeating caused by various endogenous substances or stress in free feeding rats. The physiological significance of the neuropeptide-Y-induced eating and its control by (+)-fenfluramine remains to be elucidated.

Muscarinic receptor antagonism causes a functional alteration in nucleus accumbens μ-opiate-mediated feeding behavior

Intra-nucleus accumbens (Acb) infusion of cholinergic muscarinic antagonist, scopolamine (10 μg/0.5 μl), markedly reduced fat intake elicited by intra-Acb treatment of the μ-opioid receptor agonist, DAMGO, with 30 min and 4 h pretreatment intervals. Intra-Acb scopolamine infusions also reduced food intake in food-deprived rats, but not water intake in water-deprived rats. Hence, Acb muscarinic manipulations exhibit some specificity for feeding, perhaps via interactions with the striatal opioid system.

Interactions between neuropeptide S and corticotropin releasing factor in the control of palatable food intake in rats.

Neuropeptide S (NPS) is a recently identified 20 aminoacid peptide widely distributed in the brain. NPS receptors are highly expressed in the amygdala, thalamus, hypothalamus and in cortical areas. Recently, NPS has been shown to reduce voluntary food intake in food-deprived rats. The present study evaluated the effect of NPS on palatable food consumption. Male Wistar rats were trained to consume sweetened mesh palatable food 60 min a day twice a week. Drug testing begun after stable baseline of palatable food consumption was established (4–6 presentation). NPS (0.0, 0.1, 0.3, 1.0 and 3.0 nmol/rat) was administered into the lateral cerebroventricle (ICV) 10 min before access to palatable food, and food intake was monitored 15, 30 and 60 min later. Results showed a significant inhibition of food consumption for the entire period of observation (p p

Central 5-HT 3 receptors and water intake in rats

In the present paper, we studied in rats the effect of third ventricle administration of m-chlorophenylbiguanide hydrochloride (1-(3-chlorophenyl)biguanide ( m-CPBG), a selective 5-HT 3 agonist, on water intake induced by three different physiological stimuli: water deprivation, acute salt load and hypovolemia. Central acute m-CPBG injections in the doses of 80 and 160 nmol significantly reduced water intake elicited by an acute salt load. Third ventricle injections of m-CPBG in the dose of 160 nmol significantly inhibited water intake in hypovolemic animals, whereas third ventricle injections of m-CPBG in a higher dose (320 nmol) were necessary to decrease water intake in water-deprived rats. Pretreatment with 1-methyl- N-[8-methyl-8-azabicyclo(3.2.1)-oct-3-yl]-1 H-indazole-3-carboxamide (LY-278,584), a selective 5-HT 3 antagonist, abolished the inhibitory effect on water intake seen after central administration of m-CPBG in all groups studied. The central administration of m-CPBG was also able to inhibit water intake induced by pharmacological activation of central cholinergic and angiotensinergic pathways. Third ventricle injections of m-CPBG in the highest dose employed in this study (320 nmol) were unable to modify food intake in food-deprived rats. An aversion test has shown that acute third ventricle injections of m-CPBG do not induce illness-like effects that could explain the water intake inhibition here observed. Also, central administration of m-CPBG did not modify the intake of a “dessert” meal consisting of diluted condensed milk. It is concluded that central 5-HT 3 receptor activation exerts a specific inhibitory effect on water intake.

Ipsapirone suppresses food intake in food-deprived rats by an action at 5-HT 1A receptors

The effects of the 5-HT 1A receptor agonist ipsapirone (2.5–10 mg/kg, s.c.) on food intake were investigated in rats that had been fasted for 22 h. Ipsapirone administered immediately prior to presentation of food produced a dose-related decrease in food intake. The effect of ipsapirone (5 mg/kg) was reversed by pretreatment with the 5-HT 1A receptor antagonist N-{2[4-)2-methoxyl)-1-piperazinyl]ethyl}- N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100635) (0.3 mg/kg, s.c.). The results of this study show that ipsapirone has acute dose-dependent depressant effects on food intake in fasted rats, mediated by 5-HT 1A receptors.

Effects of a nitric oxide synthase inhibitor on hypophagia induced by the peripheral 5-HT receptor agonists, alpha-methyl-5-hydroxytryptamine and 5-carboxamidotryptamine in rats.

We investigated the effects of the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on hypophagia in rats elicited by alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) and 5-carboxamidotryptamine (5-CT) which are suggested to be mediated by the peripheral 5-HT2A and 5-HT7 receptor, respectively. Both alpha-methyl-5-HT and 5-CT apparently inhibited food intake in food-deprived rats. L-NAME significantly enhanced alpha-methyl-5-HT-elicited hypophagia, while it inhibited 5-CT-elicited hypophagia. These results suggest that NO is differentially related to alpha-methyl-5-HT and 5-CT-induced hypophagia and that NO may play a role in hypo- and hyperphagia.

Differential influence of a selective melanocortin MC 4 receptor antagonist (HS014) on melanocortin-induced behavioral effects in rats

We injected i.c.v. the natural agonist α-MSH (melanocyte-stimulating hormone) and the first selective melanocortin MC 4 receptor antagonist HS014 (cyclic [AcCys 11, d-Nal 14, Cys 18, Asp-NH 2 22]-β-MSH(11–22) in rats and scored a number of behavioral effects which have been related to the melanocortic peptides. The results showed that HS014 (5 μg/rat) completely blocked α-MSH (3 and 5 μg/rat)-induced grooming, yawning and stretching. Penile erections induced by α-MSH were, however, only partially blocked by HS014. Injections of α-MSH decreased food intake in food-deprived rats, whereas HS014 increased food intake. When the peptides were given together, the food intake was similar to that of saline treated controls. Locomotion/exploration and resting were not influenced by either peptide. Our data show that exogenous α-MSH decreases food intake, and that an endogenous central melanocortinergic inhibitory tone on feeding prevails which can be blocked with HS014, leading to an increase in food intake. Our data also provide evidence that grooming, stretching and yawning in rats may be mediated by the melanocortin MC 4 receptor, whereas penile erections might perhaps be mediated by some other melanocortin receptor.

Central injection in rats of α-melanocyte-stimulating hormone analog: effects on food intake and brain Fos

Lateral cerebroventricular (LCVT) administration of the α-MSH agonist analog Nle 4DPhe 7α-MSH (NDP-MSH) inhibited food intake in food-deprived rats, but did not inhibit water intake in water-deprived rats. When NDP-MSH was administered into the fourth ventricle (4CVT), comparable suppressions of food intake were observed. LCVT and 4CVT administration of NDP-MSH also reduced spontaneous 24 h food intake. LCVT injection of NDP-MSH greatly attenuated food intake stimulated in sated rats by acute CVT administration of neuropeptide Y (NPY). These and other data suggest that α-MSH is an important endogenous regulator of food intake, possibly acting downstream of NPY. In an attempt to assess further the sites of action of NDP-MSH, a qualitative mapping study of Fos-like immunoreactive (Fos-ir) neurons was performed following LCVT administration of NDP-MSH. LCVT injection of NDP-MSH induced Fos-ir in several forebrain regions including cortex, striatum, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus and arcuate nucleus. The combination of NPY and NDP-MSH did not produce obvious antagonism or cancellation of effects in any region examined. Thus, the site(s) of action of NDP-MSH on food intake remain to be clarified.

Sensitivity of Brain Sites to the Inhibitory Effect on Alcohol Intake of the Tachykinin Aminosenktide

The present study evaluated the sensitivity of several brain sites to the inhibitory effect of the tachykinin (TK) NK-3 receptor agonist aminosenktide (NH 2-SENK) on 10% ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring rats. Attention was focused on limbic structures involved in alcohol-seeking behavior and endowed with TK NK-3 receptors. NH 2-SENK was bilaterally injected into the shell of the nucleus accumbens (NACC), the medial amygdala (AMY), the dorsal hippocampus (HIPP), the ventral tegmental area (VTA), the bed nucleus of the stria terminalis (BNST), the lateral hypothalamus (LH), and the nucleus basalis magnocellularis (NBM). NH 2-SENK (injected up to 25–75 ng/site) into the NACC, AMY, HIPP, and VTA did not significantly modify ethanol intake. Injection of NH 2-SENK into the BNST reduced ethanol intake at doses of 25 ng/site or higher, but the same doses also reduced water intake in water-deprived rats and food intake in food-deprived rats. Injection of NH 2-SENK into the LH or the NBM at doses of 0.5, 5, or 25 ng/site inhibited 10% ethanol intake even at the lowest dose tested without affecting either food or water consumption in deprived animals. Present results indicate that the LH and the NBM are highly sensitive to the inhibitory effect of the TK NK-3 receptor agonist NH 2-SENK on ethanol intake. TK peptides have been shown to evoke conditioned place preference following injection in the LH or the NBM, suggesting that in these brain sites the effect of TK agonists on ethanol intake might be due to interference with reward processes.

Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats

Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1–510 pmol/rat (0.004–2 μg/rat) ICV] and CGRP [1–131 pmol/rat (0.004–0.5 μg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 μg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC 50 = 2 pmol/rat (0.007 μg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 μg/rat)] with regard to its anorectic effect. A lesion in the AP/NTS region did not influence the anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the anorectic effects of both peptides when administered via this route.

Effects of peripheral 5-HT 2 and 5-HT 3 receptor agonists on food intake in food-deprived and 2-deoxy- d-glucose-treated rats

Peripherally administered, the 5-HT 2 receptor agonist, α-methyl-5-hydroxytryptamine (α-methyl-5-HT), significantly suppressed the food intake of food-deprived rats. α-Methyl-5-HT also inhibited 2-deoxy- d-glucose-induced hyperphagia in rats. The α-methyl-5-HT-induced hypophagia was antagonized by the 5-HT 2A receptor antagonist, ketanserin. The α-methyl-5-HT-induced decrease in food intake of food-deprived rats was not inhibited by prior adrenodemedullation. The peripheral 5-HT 3 receptor agonist, 2-methyl-5-HT, did not affect food intake in food-deprived or 2-deoxy- d-glucose-treated rats. These results suggest that the peripheral 5-HT 2A receptor may participate in the regulation of food intake and that its hypophagic effects are not associated with its adrenaline-releasing effects from the adrenal gland. Lastly, the peripheral 5-HT 3 receptor did not participate in feeding control.

Intracerebroventricular enterostatin stimulates food intake in non-food-deprived rats.

Previous studies reported that ICV enterostatin reduced high-fat food intake in food-deprived rats. The present study sought to determine if ICV enterostatin would decrease intake of a high-fat food in non-food-deprived rats. Eight doses (0-32 micrograms) were tested. Enterostatin (32 micrograms) significantly stimulated cookie intake at 30 min. Enterostatin did not reduce food intake at any dose. These results conflict with previous reports and suggest that central enterostatin does not play a role in suppressing, but may play a role in stimulating, high-fat food consumption in non-food-deprived rats.

Intracerebroventricular enterostatin stimulates food intake in non-food-deprived rats

Previous studies reported that ICV enterostatin reduced high-fat food intake in food-deprived rats. The present study sought to determine if ICV enterostatin would decrease intake of a high-fat food in non-food-deprived rats. Eight doses (0-32 micrograms) were tested. Enterostatin (32 micrograms) significantly stimulated cookie intake at 30 min. Enterostatin did not reduce food intake at any dose. These results conflict with previous reports and suggest that central enterostatin does not play a role in suppressing, but may play a role in stimulating, high-fat food consumption in non-food-deprived rats.

Temperature, food intake, and locomotor activity effects of a 5-HT3 receptor agonist and two 5-HT3 receptor antagonists in rats.

This study investigated three physiologic functions known to be modulated by serotonin-temperature, food intake and locomotor activity - using the 5-HT3 receptor agonist, m-chlorophenylbiguanide (m-CPBG), and two 5-HT3 antagonists, MDL-72222 and ondansetron. m-CPBG produced dose-dependent elevations in rectal temperature. MDL-72222, which had no effects on temperature when given alone, significantly attenuated m-CPBG-induced hyperthermia. Food intake in food-deprived rats was reduced during the first hour by the highest dose of m-CPBG. Food intake was also dose-dependently reduced by MDL-72222; m-CPBG plus MDL-72222 led to greater reductions in food intake. Food intake in freely fed rats was unaffected by m-CPBG or MDL-72222. Locomotor activity was unaffected by m-CPBG, but was dose-dependently reduced by MDL-72222, an effect which may have contributed to its hypophagic effects. Ondansetron, used in ten-fold lower doses than MDL-72222, was inactive in all of these paradigms. These data: (1) provide some evidence for 5-HT3 receptor-mediated changes in temperature; (2) are in agreement with two prior studies which reported locomotor activity reductions following 5-HT3 antagonists; but (3) do not support an important role for 5-HT3 receptors in the regulation of food intake in rats.

Parametric studies of selective D1 or D2 antagonists: effects on appetitive and feeding behaviour.

Dopamine receptor antagonists have long been known to suppress food intake. The main purpose of the present series of experiments was to investigate feeding in rats across several paradigms evaluating the effects of selective dopamine D1 and D2 antagonists. The selective D1 antagonist, SCH 23390, reduced FR8 operant responding for food (0.03mg/kg, s.c.) at a dose lower than that required to reduce food intake in two free-feeding situations (0.1mg/kg, s.c.). The selective D2 antagonist, YM 09151-2, had a biphasic effect on food intake in food-deprived rats, increasing food intake at a low dose (0.01mg/kg, i.p.), but decreasing intake at higher doses in deprived rats (0.1mg/kg, i.p.). A combination of subthreshold doses of SCH 23390 and YM 09151-2 resulted in a significant reduction in food intake. In nondeprived rats eating palatable food and in animals trained on an FR8 schedule of reinforcement, YM09151-2 exerted significant suppressant effects. The results suggest that the operant response is more sensitive to the effects of selective D1 and D2 antagonism than is the consummatory response. The findings also suggest a specific inhibitory role for dopamine D2 (and not D1) receptors on food intake, since selective D1 antagonism did not produce increases in food intake at any of the doses tested. This provides evidence that under some circumstances the effects of D1 and D2 receptor blockade are dissociable.

Selective agonists at NK3 tachykinin receptors inhibit alcohol intake in Sardinian alcohol-preferring rats

The present study evaluated the effect of tachykinin agonists, selective for different neurokinin (NK) receptors, on alcohol intake in genetically selected, Sardinian alcohol-preferring rats. Tachykinins were given by intracerebroventricular injection just before access to fluids. In rats offered both water and 8% ethanol 2 h/day, the NK3 selective agonists [Asp 5,6,MePhe 8]substance P(5–11), Suc-[Asp 6,MePhe 8] substance P(6–11), and [MePhe 7]neurokinin B markedly suppressed alcohol intake. The NK1 selective agonist [Sar 9,Met(O 2) 11]substance P and the NK2 selective agonist GR 64349 did not reduce alcohol intake. At doses that inhibited alcohol intake, the NK3 agonists did not modify water intake; total fluid intake was significantly reduced only following 500 ng/rat of [Asp 5,6,MePhe 8]substance P(5–11). When rats were given a longer access to fluids (8% alcohol for 2 h, but water for 4 h), again, NK3 agonists suppressed alcohol intake, but not total fluid intake. Moreover, NK3 agonists did not modify solid food intake in food-deprived rats, nor water intake in water-deprived rats, when alcohol was not available. These findings indicate that NK3 agonists inhibit alcohol intake in Sardinian alcohol-preferring rats and that their effect is behaviorally selective. They also suggest that central NK3 receptors may be involved in alcohol intake control in rats.

Role of serotonin receptors in the effect of sertraline on feeding behaviour.

The effect of sertraline, a serotonin (5-HT) uptake inhibitor, on 1 h food intake of food-deprived rats was studied in male rats treated intraperitoneally with 1 and 2.5 mg/kg metergoline, a 5-HT1 and 5-HT2 receptor antagonist, 0.5 mg/kg GR 38032F, a 5-HT3 receptor antagonist, or intracerebroventricularly with 6-hydroxy-dopamine to destroy catecholamine-containing neurons. The feeding-suppressant effect of 10 mg/kg sertraline was not significantly modified by any treatment. At 1 and 2.5 mg/kg metergoline did not significantly modify the reduction in total intake and meal size induced by sertraline in slightly-deprived rats whereas at 1 mg/kg the 5-HT receptor antagonist completely blocked the effect of 1.5 mg/kg d-fenfluramine, a 5-HT releaser and uptake inhibitor. In a runway test, metergoline at 1 but not 2.5 mg/kg significantly attenuated the effect of 10 mg/kg sertraline on starting speed in the first and second trial blocks. Both doses tended to attenuate the effect of sertraline on running speed but the interaction was not significant. The reduction in food intake induced by sertraline was antagonized only by 1 mg/kg metergoline in the last trial block. The bulk of these findings argues against an important role of 5-HT receptors in the effect of sertraline on feeding behaviour.

Effects of the 5-HT1A agonist 8-OH-DPAT on food intake in food-deprived rats.

The effects of 8-OH-DPAT were investigated on food intake in food-deprived rats in both non-operant and operant feeding paradigms. 8-OH-DPAT produced dose-related reductions in food intake in both paradigms. While the higher doses of 8-OH-DPAT used in this study (i.e. 125-500 micrograms kg-1) produced a number of stereotyped behaviours which may have interfered with normal feeding, these behaviours were not apparent with the lower doses (i.e. 15.625-62.5 micrograms kg-1) which also depressed food-intake. The results of this study thus suggest that the inhibitory effect of 8-OH-DPAT on feeding in food-deprived rats is not secondary to the induction of stereotypy.

Chapter 28 Cholecystokinin in the control of ingestive behavior

Publisher Summary Cholecystokinin octapeptide (CCK-8) is a peptide released from the duodenum during a meal that inhibits food intake in food-deprived rats, and the associated suggestion that CCK-8 may be a peripheral satiety factor of physiological relevance gave a new perspective in that the importance of gut–brain interactions is realized. This chapter describes the peptidergic control of ingestive behavior. The chapter also addresses several important issues, such as does inhibition of ingestive behavior occur in the presence of physiological plasma levels of CCK? Is the effect of CCK-8 on ingestive behavior a specific one or does it reflect a pharmacologically activated artificial mechanism? and what is the role of central neural CCK in the regulation of food intake? The CCK-8 hypothesis of satiety is physiologically relevant. The brain mechanism that terminates the ingestion of food uses CCK as a transmitter. However, the views expressed in this chapter are overly simplistic, because the contributions of a variety of other transmitters, which undoubtedly contribute to normal feeding and to the mechanism of action of CCK-8, have been ignored.