Effects of subcutaneous administration of the gamma-aminobutyric acid(A) receptor agonist muscimol on water intake in water-deprived rats

The effects of the gamma-aminobutyric acid(A) (GABA(A)) receptor agonist muscimol were investigated on water intake in rats that had been deprived of water for 16 h. Muscimol (0.5-2.0 mg/kg sc) produced a dose-related inhibition of water consumption in both male (n=8) and female (n=8) rats, with maximal suppression of drinking occurring during the first 30 min after administration. Doses of 1 and 2 mg/kg produced significant decreases in water intake (P<.01), while a lower dose of 0.5 mg/kg was without effect. The hypodipsic effect of muscimol (1.0 mg/kg sc) was abolished by pretreatment of the animals with the GABA(A) receptor antagonist bicuculline (1 mg/kg sc). Furthermore, muscimol (2 mg/kg sc) did not produce aversion in a two-bottle conditioned taste aversion test, indicating that the suppressant effects of muscimol on water intake are not due to drug-induced malaise. The results suggest that systemic administration of muscimol produces a behaviourally specific suppression of primary drinking in rats by a GABA(A) receptor-mediated mechanism. Moreover, this action of muscimol appears to be independent of the gender of the animals.     

Lesions of the MPO or AV3V: influences on fluid intake

Electrolytic lesions in the MPO of rats had no significant effects on ad lib food and water intake, but impaired the drinking response to 1 M NaCl. Large MPO lesions also produced a persistent increase in plasma osmolality. In Experiment 2, we depleted neurons from the MPO of rats by iontophoretic application of the neurotoxin kainic acid (KA) which destroys nerve cell bodies without damage to fibers of passage. KA-induced neuron depletion in the MPO of rats significantly reduced the drinking response to 1.0 M saline, to 30% PG, and to 30 micrograms/kg isoproterenol. Ad lib water intake and drinking responses to food or water deprivation, to low concentrations (0.5 M) of hypertonic saline, to low concentrations (10% or 20%) of PG, and to systemic administration of 1.5 mg/kg angiotensin II were within the normal range. In Experiment 3, rats with electrolytic lesions that were strictly confined to the tissue immediately surrounding the wall of the anteroventral portion of the third ventricle (AV3V), without invading the MPO displayed normal ad lib food and water intake and plasma osmolality as well as drinking responses to water deprivation, hypertonic saline (0.5 or 1.0 M), angiotensin II (1.5 mg/kg) and isoproterenol (30 micrograms/kg).     

Specific effect of putative 5-HT1A agonists, 8-OH-DPAT and gepirone, to increase hypertonic saline consumption in the rat: evidence against a general hyperdipsic action

Previous reports indicate that 5-HT1A agonists, in addition to benzodiazepines, increase the consumption of hypertonic saline in rehydrating rats. Experiment 1 investigated the effects of 8-OH-DPAT (10-100 micrograms/kg) and gepirone (0.1-3.0 mg/kg) on consumption of water and of saline over a range of concentrations (0.45%-2.8%) in a 30 min drinking test. The two 5-HT1A agonists dose-dependently increased ingestion of two hypertonic salt solutions, but produced little or no increase in the drinking of water, hypotonic or isotonic saline. Experiment 2 demonstrated that 8-OH-DPAT and gepirone did not enhance water consumption in animals given a water preload, or markedly increase drinking quinine-adulterated water. Taken together, the results indicate a selective dose-related effect of the two drugs to increase hypertonic saline drinking; they did not have a general hyperdipsic effect across all salt and water conditions, and they did not increase intake simply because of a low baseline level of consumption. Hence, 5-HT1A agonist act much more selectively than benzodiazepines in their effects on drinking responses.     

Histaminergic mechanism for drinking elicited by insulin in the rat

Sprague-Dawley male albino rats showed in a dose-response study a maximal drinking response to a 5 U/kg dose of SC insulin in a 2-hr test. Drinking elicited by 5 U/kg insulin was reduced to baseline (i.e., no insulin) level by combined antagonism of H1 and H2 receptors for histamine using IP 1 mg/kg dexbrompheniramine plus 16 mg/kg cimetidine. Antagonism of histamine receptors in this fashion was specific for drinking elicited by histamine because such antagonism reduced to baseline level drinking elicited by 2.5 mg/kg SC histamine, but failed to inhibit drinking after 8- or 24-hr water deprivation or drinking after 0.63 mg/kg SC serotonin (5-HT). These results demonstrate a histaminergic mechanism for drinking elicited by exogenous insulin which is consistent with the published report that exogenous insulin can release gastric mucosal histamine in the rat. Moreover, because eating is known to elicit the release of endogenous insulin, the results reported here suggest a working hypothesis that endogenous insulin is a component for drinking around mealtime in the rat.     

Consistency of cholecystokinin satiety effect across deprivation levels and motivational states

A gastrointestinal hormone, cholecystokinin (CCK), has recently been implicated in the regulation of meal size. The consistency of the CCK satiety effect was examined across deprivation levels and motivational states. In a series of experiments rats were food deprived for varying amounts of time and injected with various doses of the CCK octapeptide before consuming a test meal of a liquid diet. In Experiment 1, 20 rats were deprived for 5 or 19 hr and injected with 0, 15, and 40 Ivy dog units/kg (U/kg) of CCK and in Experiment 2, 18 rats were 48 hr deprived and were injected with 0, 40, or 80 U/kg of CCK. In Experiment 3, 12 rats were deprived for 92 hr and received 80 U/kg of CCK. In all experiments CCK produced a dose-related suppression in food intake. CCK did not appear to become less effective as deprivation increased: 15 U/kg suppressed intake by approximately 30% at 5 and 19 hr deprivation; 40 U/kg suppressed intake by approximately 50% at all three deprivation levels; 40 U/kg suppressed intake by approximately 72% at 48 hr deprivation and 66% at 92 hr deprivation. In Experiment 4, the effects of CCK on food consumed in absence of hunger (0 hr deprivation) were observed by administering hypertonic saline to food-sated rats before presentation of a liquid diet. Under these conditions 40 U/kg of CCK suppressed intake by 76%. An additional experiment indicated that the increased inhibitory effects observed in the latter experiment were not due to the added variable of thirst. Thus under a wide variety of deprivation conditions and under varying motivational states CCK is remarkably consistent in its inhibitory effects on food intake, which are best described by a constant percent of control intake.     

Effect of the H1-histamine receptor agonist betahistine on drinking and eating behavior in pygmy goats.

The effect of different doses of the H1-receptor agonist betahistine (0.9 and 2, 4 and 8 mg/kg b.wt.(0.75)) on water and food intake was investigated in 12 pygmy goats. Intraperitoneal (i.p.) injection of betahistine (2, 4, and 8 mg/kg b.wt.(0.75)) stimulated drinking in a dose-dependent manner. Food intake was decreased after the injection of 4 or 8 mg/kg b.wt.(0.75) betahistine, respectively. The increase in water intake was characterized by an increased draft size and decreased latency to drink. The decrease in food intake at the highest dose tested was characterized by an increased latency to eat and by a decreased meal frequency, and food intake associated to drinking was decreased. In line with previous studies, these results support the hypothesis that food-associated drinking is mediated by stimulation of H1-receptors of histamine in pygmy goats.     

Calcitonin effect on the dipsogenic response to intra-cerebroventricular administration of angiotensin II

Evidence indicates that intra-third cerebroventricular (III-ICV) administration of calcitonin suppresses food and water intake of rats. The purpose of this study was to determine whether calcitonin would influence angiotensin II-induced dipsogenesis when simultaneously administered III-ICV. Administration of calcitonin (0.5 U/rat) suppressed food and water intake in male Wistar rats. III-ICV administration of angiotensin II (100 ng/rat) to rats provided with ad lib food and water elicited short latency drinking without affecting food intake. III-ICV administration of calcitonin (0.5 U/rat) did not affect the drinking-inducing response to 100 ng/rat of angiotensin II when administered simultaneously. The results suggest that decrease in water intake by III-ICV calcitonin may be a consequence of the food intake suppression, i.e., reduced prandial drinking.     

Food intake and behavioral caloric compensation after protein repletion in the rat

The food intake response of rats to intragastrically infused or orally consumed protein was characterized and compared to the response to similarly administered carbohydrate. In Experiment 1, protein hydrolysate loads administered at the beginning of the dark phase via chronic intragastric cannulae led to rapid (complete within 3–4 hr), dose-related suppressions of food intake in comparison to sham loads or to urea loads controlling for volume, concentration and pH. The suppression remained evident in cumulative intake records through 24 hr and represented a greater than caloric compensation for the amount of metabolizeable energy delivered (1.38 and 1.12 kcal/kcal in Experiments 1a and 1b, respectively). In Experiment 2, protein hydrolysate loaded by gavage suppressed food intake significantly more than isocaloric glucose loads (1.32 vs 0.81 kcal/kcal after 24 hr). Water intake in both experiments was elevated by protein loads, although this occurred after the food intake suppression. Differential satiety responses to protein and carbohydrate repletion were shown in Experiment 3 to extend to orally consumed, naturally occurring macronutrients—casein vs starch and disaccharide diets. These data suggest that satiety in the rat is not solely graded with respect to the energy delivered by the preceding meal but rather that repletion with different macronutrients leads to quantitatively (or perhaps qualitatively) different satieties.     

The effect of dexamethasone-21-acetate on meal size, meal frequency and macronutrient self-selection in rats

In Experiment 1, the measurement of 24-hour food intake in two rats showed that treatment with dexamethasone-21-acetate (DEX) (0.5 mg/kg IP) produced a decrease in body weight which was at least partially due to a decrease in food intake (both meal frequency and meal size). In Experiment 2, the daily intake of three macronutrient sources was measured. These data showed that treatment with DEX (0.5 and 1.0 mg/kg IP) led to an acute increase in protein intake, a sustained decrease in fat intake and no change in carbohydrate consumption. We suggest that this change in macronutrient selection may be an adaptive response which serves to ameliorate some of the effects of DEX treatment.     

Histamine plays a major role for drinking elicited by spontaneous eating in rats

The effects of combined antagonism of H, (using 1 mg/kg dexbrompheniramine IP) and H₂ (using 16 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 1-hr water deprivation, and (c) drinking during spontaneous eating were examined at 1 hr into the dark phase of a 12:12′-hr light/dark cycle for 14 Sprague-Dawley male rats. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without affecting drinking after water deprivation. Histaminergic antagonism did not affect spontaneous eating, but it appeared to abolish drinking prior to a meal (for only those 3 rats which exhibited such drinking), delayed the latency to initiate drinking after initiating a meal, and inhibited drinking which occurred during and after eating but prior to postprandial resting (i.e., satiety for food). Because antagonism of peripheral histamine receptors inhibited food-related drinking by over 60%, these results provide indirect support for the hypothesis that the preabsorptive food-contingent vagally-mediated release of gastric mucosal histamine plays a major role in spontaneous food-related drinking in the rat.     

Central bombesin inhibits food intake and the orexigenic effect of neuropeptide Y in the neonatal chick

It is well known that central injection of bombesin (BN) suppresses feeding in mammalian and avian species, but the anorexigenic effect of central BN are still open with special reference to the chick. The dose response (0, 0.1 and 0.5 μg) of intracerebroventricular (ICV) injection of BN was examined in Experiment 1. ICV injection of BN inhibited food intake in a dose-dependent manner. Experiment 2 was done to determine whether BN interacts with the orexigenic effect of neuropeptide Y (NPY) in the neonatal chick. Central administration of NPY (2.5 μg) greatly enhanced food intake, but co-injection of BN (0.5 μg) suppressed food intake. The dose response of NPY (2.5 μg) co-injected with three levels of BN (0, 0.1 and 0.5 μg) was examined in Experiment 3. ICV injection of BN attenuated the hyperphagia by NPY in a dose-related fashion. It is suggested that central BN may interact with NPY for the regulation of feeding in the neonatal chick.     

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

The effects of the 5-HT1A agonist 8-hydroxy-2 (di-n-propylamino)tetralin (8-OH-DPAT) were investigated on operant food intake in food-deprived pigs. In Experiment 1, 8-OH-DPAT (5-20 microg/kg) administered intravenously (i.v.) 15 min prior to the occurrence of feeding produced a dose-related decrease in operant food intake in pigs that had been fasted overnight. The effects were mainly apparent during the first 30 min after the start of the feeding period. In Experiment 2, 8-OH-DPAT (25 and 50 microg/kg, i.v.) administered 60 min prior to the occurrence of feeding in pigs that were fasted overnight also produced significant decreases in food intake. The effects were mainly apparent during the first 30-40 min after the start of the feeding period. In Experiment 3, 8-OH-DPAT (20 microg/kg, i.v.) significantly increased operant feeding in satiated pigs during the first 30 min after administration. These results show that 8-OH-DPAT has complex effects on feeding behaviour in pigs, increasing operant food intake in satiated pigs, while producing a reduction in food intake in food-deprived animals.     

Effects of 4-hydroxyamphetamine on in vivo brown adipose tissue thermogenesis and feeding behavior in the rat

The influence of 4-hydroxyamphetamine (4-OHAM) on food and water intake and in vivo brown adipose thermogenesis was examined in two experiments. In Experiment 1, female rats were treated with 0.00, 0.25, 0.50, 1.00, or 2.00 mg/kg 4-OHAM (ip) prior to assessment of interscapular brown adipose tissue (IBAT) thermogenesis. The 4-OHAM treatment induced dose-dependent activation of IBAT thermogenesis consistent with the enhanced serum levels of norepinephrine and epinephrine observed in 4-OHAM-treated rats immediately after temperature measurement. In Experiment 2, the influence of 4-OHAM on food and water intake was assessed during 120-min test intervals in female rats fed food and water ad lib. Although there was a trend for 4-OHAM to increase water intake, there was no significant effect of 4-OHAM (0.40, 0.80, 1.00, 2.00, and 4.00 mg/kg) on either food or water intake. These data suggest that brown adipose thermogenesis does not play a role in the anorexia induced by amphetamine or in the regulation of feeding.     

Kappa opioid binding sites in the dog cerebral cortex and spinal cord

In the dog cerebral cortex and spinal cord, [3H]bremazocine and [3H]U69593 both bound with high affinity to an apparent single population of binding sites under kappa-selective conditions. In the cortex similar Bmax values for both radioligands in the saturation studies and the high affinity of the kappa-selective agents PD117302 and U69593 for both [3H]bremazocine and [3H]U69593 labelled sites in the competition studies suggested a predominance of U69593-sensitive sites previously described as kappa 1 in the guinea-pig and rat brain. The lower slope values for the inhibition curves of PD117302 and U69593 against [3H]bremazocine but not against [3H]U69593 suggested that [3H]bremazocine could also be binding to a relatively minor proportion of additional, possibly kappa 2, sites while [3H]U69593 would appear to be selective for the kappa 1 site. In contrast, in the dog spinal cord, [3H]U69593 appeared to recognize only a proportion (approximately 35%) of the [3H]bremazocine labelled binding site. The significantly lower affinities and slope values of U69593 and PD117302 against [3H]bremazocine were consistent with the additional sites representing the k2 (benzomorphan) sites previously described in guinea-pig and rat spinal cord. Alternatively, the low (micromolar) affinity of the mu-selective ligand, [D-Ala2, MePhe4, Gly-ol5]enkephalin, implied that these additional sites might not be kappa 2 but possibly a low affinity mu site normally expressed under more physiological conditions.     

Histamine plays no part in schedule-induced polydipsia in the rat

Twelve Sprague-Dawley male albino rats were tested with or without combined antagonism of peripheral H1 (using 2 mg/kg dexbrompheniramine IP) and H2 (using 32 mg/kg cimetidine IP) receptors for histamine prior to (a) drinking after 2.5 mg/kg histamine SC, (b) drinking after 24-hr water deprivation, and (c) drinking during the acquisition and maintenance of schedule-induced polydipsia (SIP) with a 45 mg Noyes pellet delivered every 90 sec. Such antagonism of histamine receptors abolished drinking elicited by exogenous histamine without inhibiting drinking after water deprivation. Moreover, histaminergic antagonism failed to prevent the acquisition and maintenance of SIP and failed to alter the distribution of contacts with the drinking spout during interpellet intervals. These findings demonstrate no role for endogenous systemic histamine in SIP.     

Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

κ-Opioid receptor stimulation attenuates psychostimulant-induced increases in extracellular dopamine in the caudate–putamen (CPu) and nucleus accumbens of adult rats, while reducing cocaine-induced locomotor activity and stereotyped behaviors. Because κ-opioid receptor agonists (e.g., U50,488 or U69,593) often affect the behavior of preweanling rats in a paradoxical manner, the purpose of the present study was to determine whether κ-opioid receptor stimulation differentially affects dopaminergic functioning in the CPu depending on age. In vivo microdialysis was used to determine whether U50,488 (5 mg/kg) attenuates cocaine-induced dopamine overflow in the dorsal CPu on postnatal day (PD) 17 and PD 85. In the microinjection experiment, cocaine-induced stereotyped behaviors were assessed in adult and preweanling rats after bilateral infusions of vehicle or U50,488 (1.6 or 6.4 μg per side) into the CPu. Results showed that U50,488 attenuated the cocaine-induced increases in CPu dopamine overflow on PD 85, while the same dose of U50,488 did not alter dopamine dialysate levels on PD 17. Cocaine also increased stereotyped behaviors (repetitive motor movements, behavioral intensity scores, and discrete behaviors) at both ages, but adult rats appeared to exhibit more intense stereotypic responses than the younger animals. Consistent with the microdialysis findings, bilateral infusions of U50,488 into the dorsal CPu decreased the cocaine-induced stereotypies of adult rats, while leaving the behaviors of preweanling rats unaffected. These results suggest that the neural mechanisms underlying κ-opioid/dopamine interactions in the CPu are not fully mature during the preweanling period. This lack of functional maturity may explain why κ-opioid receptor agonists frequently induce different behavioral effects in young and adult rats.     

Characterization of central actions of neuropeptide Y on food and water intake in rabbits

The effects of a 36-amino acid peptide, neuropeptide Y (NPY), on feeding and drinking behaviors were studied in young and adult rabbits. Intraventricular injection of NPY to adult rabbits induced feeding and drinking in a dose-related manner. While the lowest doses tested (0.2 micrograms) was without effect, other doses (0.5 and 1 microgram) elicited feeding and drinking almost instantaneously. When 1, 5 and 10 microgram doses were injected into young rabbits, immediate increases in feeding and drinking were evident, but differences in the magnitude of responses among these dosages were significant only in water consumption. Unlike studies in rats, in these rabbits NPY elicited a more pronounced response in drinking than in feeding. The drinking response after NPY administration was not a consequence of food intake because it occurred in the absence of food. With ad lib feeding, the majority of enhanced food consumption was confined to the first 30-min after NPY injection; however, an increased motivation to eat was retained for at least 2 hr after NPY when food was withheld and then returned. These observations are consistent with specific stimulatory effects of NPY on food and water intake.     

Effects of maternal state on the responsiveness to nest odors of hooded rats

Systemic antagonism of H1 or H2 receptors for histamine attenuated drinking elicited by SC 20 mg/kg histamine in adult male Sprague-Dawley rats. The H1 antagonist dexbrompheniramine (DXB; 0.5-16 mg/kg) and the H2 antagonist cimetidine (C; 0.5-100 mg/kg) each inhibited drinking elicited by histamine when given IP 10 min prior to SC histamine: The lowest doses to produce a statistically significant inhibition of drinking were 2 mg/kg DXB and 32 mg/kg C. While 1 mg/kg DXB alone or 16 mg/kg DXB plus 16 mg/kg C virtually abolished drinking elicited by histamine (1.25-20 mg/kg) in a dose-response study. In addition, such combined antagonism of H1 and H2 receptors failed to elicit drinking in the absence of exogenous histamine and failed to inhibit drinking elicited by deprivation from water for 7 or 24 hr. Because combined systemic antagonism of H1 and H2 receptors can specifically and completely inhibit drinking elicited by exogenous histamine, these findings provide a probe for a histaminergic component of drinking in the rat.     

Oral serotonin administration affects the quantity and the quality of macronutrients selection in European sea bass Dicentrarchus labrax L

Teleost fish are able to regulate their energy intake selecting from pure macronutrients sources, but the regulatory mechanisms involved in macronutrients selection remain unknown. Serotonin (5-HT) reduces food intake in mammals and fish and modifies the macronutrients selection pattern in mammals; however, no information is available about its role on macronutrients selection in fish. The aim was to determine the effect of orally administered 5-HT (0.1, 0.5 and 2.5 mg kg BW(-)(1)) into gelatine capsules on the subsequent macronutrient selection of sea bass, using for this purpose gelatine capsules including carbohydrates, protein, or lipids separately. The voluntary ingested 5-HT was released into the plasma of fish, reaching a level two times greater than the controls, 45 min after the ingestion of a capsule containing 2.5 mg kg BW(-1) of 5-HT. The indoleamine, at doses of 0.1, 0.5 and 2.5 mg kg BW(-1), produced a reduction in total food intake of 31%, 49% and 37%, respectively, compared to the baseline, modifying the macronutrient selection pattern. The percentage of fat selected was significantly reduced whereas the percentage of protein significantly increased after administration of highest dose, but no changes were observed in the proportion of carbohydrate for any 5-HT doses. In conclusion, oral administration of 5-HT affected both amount of food intake and pattern of macronutrients selected. This is the first evidence supporting a role of 5-HT as a neurohumoral mediator involved in macronutrients selection in fish.     

Effects of amylin and salmon calcitonin on feeding and drinking behavior in pygmy goats

In the present study, the effects of peripherally administered amylin and of the amylin-related peptide salmon calcitonin (sCT) on food and water intake was tested for the first time in pygmy goats. In the first series of experiments, the effect of amylin on food (0.5, 1.0 and 2.0 microg/kg b.wt.) and water (2.0 microg/kg) intake was tested. In the second series of experiments, the effect of sCT on food intake (1.0 microg/kg) was tested under ad libitum feeding conditions or after 14 h food deprivation. The relationship of dose on the effect of sCT (0.1, 0.5 and 1.0 microg/kg) on food and water intake was also tested. Finally, the effect of a low dose (0.1 sCT microg/kg) on water intake was also investigated during food withdrawal. We showed for the first time an anorexigenic effect of the satiety peptide amylin (2.0 microg/kg) in ruminants, which was characterized by a reduction in meal size. In pygmy goats, the administration of the three doses of sCT induced an anorexigenic effect, which was larger and of longer duration when compared with amylin, although the anorexigenic effect of the lowest dose never reached significance. This effect was not dose dependent and was partly due to a reduction in meal size and partly to a prolongation of the interval between meals. The anorexigenic effect of sCT was accompanied by a reduced water intake, probably due to reduced prandial drinking. Furthermore, the low dose of sCT (0.1 microg/kg) was dipsogenic during food withdrawal.