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PubMed1994

Amiloride reduces the aversiveness of acids in preference tests.

Experiments were conducted to determine the relative contribution of amiloride-sensitive pathways to the aversiveness of acid stimuli in preference tests performed on male Golden Syrian hamsters. In Experiment 1 hamsters were given a choice between water and test solutions in two-bottle preference tests lasting 4 days. The results showed that although citric acid at pH 3.0-5.0 was not aversive, at pH 1.4 or 2.0 citric acid was avoided by all animals, as indicated by both consummatory behavior and licking activity. Experiment 2 was conducted to determine whether amiloride could reduce the aversiveness of citric acid in preference tests. Citric acid at pH 2.4, an aversive solution, and citric acid at pH 3.8, which was not aversive, were tested either alone or in the presence of amiloride. Amiloride (30-300 microM), which when presented alone was neither preferred nor avoided, significantly reduced the aversiveness of citric acid at pH 2.4, similar to its effect on NaCl aversiveness. However, amiloride had no effect on intake of citric acid at pH 3.8, nor upon preference for saccharin. These results support those found in isolated hamster taste cells and from in situ taste bud recordings, which suggested that amiloride-sensitive pathways contribute to the transduction of acidic stimuli.

Amiloride↗

PubMed1981

Ethanol-Metrecal diets: I. effects of different levels of ethanol-derived kilocalories on consumption of diet, body weight and grams of ethanol ingested.

Three experiments investigated the relationship between ethanol consumption and the percentage of ethanol-derived kilocalories contained in liquid diets. Rats were chronically maintained on diets where different concentrations of ethanol (10%, 12%, 14%) were added to Metrecal so that 41%, 49% and 57% of all kilocalories consumed were derived from ethanol. The ethanol-Metrecal diet served as the sole source of calories. Results demonstrated that rats can be maintained for extended time periods on diets where ethanol contributed approximately 50% of the daily kilocalories. Inspection of consummatory profiles revealed that an initial decrease occurred in volume of diet consumed when levels of ethanol were increased. This was followed by a gradual increase in the level of consumption until a new asymptotic level was established. Grams of ethanol/kg of body weight remained relatively constant over the range of ethanol concentrations employed. The results were discussed in respect to three factors controlling consummatory behavior--sensory stimuli, caloric intake and quantity of ethanol ingested.

Acoustic Stimulation↗

PubMed1987

Quantitative assessment of tolerance development to diisopropylfluorophosphate.

Rats were treated with diisopropylfluorophosphate (DFP) acutely or daily for 14 days. The quantitative assessment of tolerance development after a challenge dose of DFP, 2 mg/kg, was studied. The subacutely-treated rats developed tolerance to DFP-induced tremors. However, the severity of tremors in DFP-tolerant animals was not significantly different from that of the controls after the challenge dose of DFP was administered. Hind-limb abduction was significantly lower in the subacutely-treated group than in the acutely-treated group. The recovery of body weights in subacutely-treated rats (3.5%/day) was significantly higher than that in acutely-treated rats (2.0%/day). The consummatory behaviors (food and water consumption) recovered faster in subacutely-treated rats than in the acutely-treated group. Body temperatures were decreased to the same extent in both groups, but the subacutely-treated group recovered faster. The total mortality was significantly lower in subacutely-treated rats (10%) than in acutely-treated rats (35%). The results further substantiate the finding that tolerance develops to various DFP-induced signs of toxicity.

Animals↗

PubMed1987

Effect of clonidine on consummatory negative contrast and on novelty-induced stress.

In Experiments 1 and 1a rats were shifted from 32% to 4% sucrose solutions. The resultant negative contrast effect in consummatory behavior was not alleviated by clonidine (3.12, 6.25, 12.5, 25.0 and 50.0 micrograms/kg). The lower dose of the drug had no effect on behavior, the higher doses reduced consumption in shifted and unshifted rats in a dose dependent fashion. In Experiment 2 clonidine (6.25, 12.5 micrograms/kg) raised plasma glucose levels in a dose dependent fashion when the animals were exposed to a novel environment. These results are at variance with those obtained with chlordiazepoxide (and other anxiolytics in the case of contrast effects) and suggest limits on the degree to which clonidine can be considered to function as an anxiolytic.

Animals↗

PubMed1989

Effects of 5-HT1A receptor agonists and L-5-HTP in Montgomery's conflict test.

The effects of the pyrimidinyl-piperazines buspirone, gepirone, ipsapirone and their common metabolite 1-(2-pyrimidinyl)-piperazine (PmP) as well as of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and L-5-hydroxytryptophan (L-5-HTP) were investigated in Montgomery's conflict test--an animal anxiety model based on the animal's inborn urge to explore a new environment and its simultaneous fear of elevated, open spaces. Subcutaneous buspirone (32-128 nmol/kg), gepirone (32-128 nmol/kg), ipsapirone (32-512 nmol/kg) and 8-OH-DPAT (50-200 nmol/kg), as well as intraperitoneal L-5-HTP (56 mumol/kg) produced anxiolytic-like effects. However, at higher doses the magnitude of these effects decreased and overall the dose-response curves displayed inverted U-shapes. The highest doses (2048 nmol/kg) of buspirone and of gepirone even decreased responding below control levels, possibly in part due to concomitant sedation/motor impairment. After L-5-HTP (448 mumol/kg) and PmP (512 nmol/kg) anxiogenic-like effects were observed. The results indicate that anxiolytic- and anxiogenic-like effects of drugs affecting central serotonergic neurotransmission can be obtained in a sensitive rat anxiety model which neither involves consummatory behavior nor punishment. The anxiolytic-like effects of these compounds may be due to their 5-HT1A agonistic properties. Moreover, the present data may provide support for a possible reciprocal association of presynaptic 5-HT1A receptors vs. postsynaptic 5-HT1A as well as 5-HT2 receptors with regard to anxiety.

5-Hydroxytryptophan↗

PubMed1990

Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference.

The effect of naloxone on voluntary ethanol intake was examined in rats which were selectively bred for oral ethanol preference (High Alcohol Drinking or HAD line). Rats of the HAD line were treated with naloxone in doses of 0.05-18.0 mg/kg b.wt. before access to water alone or to a free-choice between a 10% (v/v) ethanol solution and water. Naloxone suppressed water intake when water was presented as the sole source of fluid. In contrast, naloxone produced a dose-dependent decrease in ethanol consumption, without altering water intake, when rats were given a free-choice between the ethanol solution and water. Selective suppression of ethanol consumption by naloxone was not attributable to changes in blood ethanol concentrations or ethanol elimination rates following naloxone treatment. It appears that although naloxone may attenuate the positively reinforcing properties of both ethanol and water, ethanol drinking is a subset of consummatory behaviors that is particularly sensitive to opioid receptor blockade. The results suggest that activation of the endogenous opioid system may be an important mechanism which serves to maintain continued ethanol drinking.

Alcohol Drinking↗

PubMed1992

Microstructural analysis of the effects of THIP, a GABAA agonist, on voluntary ethanol intake in laboratory rats.

The effects of GABAA agonist THIP on the acquisition of voluntary ethanol intake and the pattern of food and water consumption were examined through the use of a computer-controlled data acquisition system. Twenty male Long-Evans rats were randomly assigned to two groups, one of which received THIP (16 mg/kg, IP) and the other an equal volume of saline. Subjects were presented with a free choice of ethanol and water immediately following drug injections, which occurred every other day. The initial concentration of ethanol presented was 2% and was increased by increments of 2% following the second presentation of each concentration, up to a maximum concentration of 10%. Subjects treated with THIP consumed significantly greater amounts of ethanol than did saline controls. A microstructural analysis of bout patterns suggested that the increased consumption of ethanol was a function of an increase in the size, duration, and frequency of ethanol drinking bouts. Food intake was also attenuated by THIP treatment. The results indicated that the decrease in total food intake was a function of a decrease in the frequency of the food bouts. However, in contrast to that observed for ethanol intake, the size and duration of the food bouts were unchanged. The qualitatively different patterns in the microstructure of consummatory behavior for ethanol and food following THIP treatment would suggest that differential mechanisms may mediate the food and ethanol effects observed in the present study. In addition, the differential effects of THIP on ethanol consumption relative to water would suggest that GABAA manipulations may play a role in influencing the acquisition of voluntary ethanol drinking.

Alcohol Drinking↗

PubMed1990

Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect.

Stimuli consistently paired with shock become capable of suppressing ongoing operant or consummatory behavior (the conditioned emotional response--CER) or elevating the amplitude of the startle reflex (fear-potentiated startle). These changes are used to infer a central state of fear which involves the central nucleus of the amygdala and its efferent projections to the brainstem. The present paper reviews how psychoactive drugs affect these measures. Both the CER and fear-potentiated startle are reduced by benzodiazepines, barbiturates and opiates. Advantages and disadvantages of these animal tests of anxiety are discussed.

Animals↗

PubMed1982

Enhanced amphetamine anorexia, but not drinking suppression in obese Zucker rats.

The effects of d-amphetamine on ad libitum consummatory behavior of genetically obese Zucker rats and their lean littermates were examined in two experiments. In Experiment 1 food intake was measured every two hours for six hours following intraperitoneal injections of 0.0, 0.5, and 1.0 mg/kg of d-amphetamine sulfate. Both lean and obese animals significantly suppressed food intake for the first two hours after injection of 0.5 and 1.0 mg/kg doses. Lean animals displayed no suppression of food intake at four or six hours after injection. In contrast to lean animals, obese rats continued to show a suppression of feeding at four hours after injection of 1.0 mg/kg. Total six-hour food intake of obese animals was significantly suppressed from baseline after 0.5 and 1.0 mg/kg of amphetamine, but only after the 1.0 mg/kg injection with lean animals. Experiment 2 examined the effects of these same doses on both food and water intake of different groups of obese and lean Zucker rats. The enhanced anorexia with the 1.0 mg/kg injection of amphetamine was replicated. Water intake, however, was suppressed only during the first two hours after both the 0.5 and 1.0 mg/kg injection in obese and lean rats. Results of the present experiments are discussed in light of previous studies of the effects of amphetamine on hypothalamically obese animals.

Animals↗

PubMedDate not supplied

Pharmacology of drug self-administration.

Limited access to drugs provides a reliable model for their acute-reinforcing effects and a means by which to explore neuropharmacological mechanisms involved in these effects. In limited access situations intravenous self-administration rates of opiates and psychomotor stimulants is inversely related to dose, and competitive antagonists at low doses increase the number of injections self-administered. Competitive agonists decrease drug self-administration. However noncompetitive antagonists tend to produce decreases in self-administration and the specificity of these results are difficult to interpret. A limited access procedure of ethanol (10% v/v) self-administration using a sucrose or saccharin fade out procedure resulted in reliable and stable ethanol (10% v/v) and water self-administration in a concurrent choice situation using nondeprived unselected Wistar and alcohol preferring P-rats. As observed by others, the opiate antagonist naloxone decreased fluid intake in both strain of rats. However, contrary to earlier results naloxone did not produce a selective decrease in ethanol preference. The serotonin antagonist methysergide had no significant effect on fluid intake or ethanol preference. However, the long-acting dopamine agonist bromocriptine decreased ethanol intake and increased water intake producing a significant decrease in ethanol preference. The results with naloxone suggest that opiate interactions with ethanol may reflect a more general effect on consummatory behavior and the results with bromocriptine suggest that the reinforcing effects of low doses of ethanol may involve a dopaminergic component. Future studies should explore further the interactions of ethanol with competitive antagonists (if possible), and fluid intake or ethanol preference with limbic-extrapyramidal circuitry involved in mediating the reinforcing actions of other drugs of abuse.

Animals↗

PubMedDate not supplied

Free-choice ethanol consumption by rats: effects of ACTH4-10.

The individual and interactive effects of immobilization stress, ACTH11-24 and ACTH4-10 on the free-choice consumption of ethanol in rats were studied. Stress and ethanol both result in activation of the HPA axis and release of ACTH1-39. The animals were offered a two-bottle choice consumption of 0.2% saccharin and 10% ethanol. They were exposed to immobilization stress or IP injections of ACTH4-10 or ACTH11-24 on an irregular, unpredictable schedule. Stress resulted in a decrease in ethanol consumption during the stress period while ACTH11-24 was devoid of any effect. The ACTH4-10 fragment produced an almost complete block of ethanol consumption during the injection period. Saccharin consumption was not affected by any of the above treatments. These results suggest an important role for ACTH4-10 (produced from ACTH1-39) in ethanol consummatory behavior in rats.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Neurobehavioral effects of the calcium ionophore A23187.

The divalent cationic ionophore A23187 (calimycin) facilitates the transport of calcium ions across biological membranes, resulting in an increase of cytosolic calcium. A23187 has been used extensively in vitro to activate calcium-dependent neurocellular processes. Because of its potential usefulness as a neurotoxicological probe, our laboratory conducted a series of studies to characterize the neurofunctional consequences of A23187 in the intact organism. In addition to approximating the LD50, the effects of acute parenteral administration of A23187 on conditioned avoidance, nociceptive shock threshold, open-field activity, consummatory behavior, body temperature and neuromotor function, including general activity, coordination, balance and grip strength, were assessed in the rodent. The LD50 of A23187, administered intraperitoneally to adult male rats, was 9.2 mg/kg. The predominant overt signs of toxicity included lethargy, limb weakness and apnea. Lower doses, from 0.5 to 0.03 mg/kg, produced a variety of more subtle neurobehavioral effects, including a selective depression of motor activity, a moderate elevation of shock threshold, altered conditioned avoidance behavior and hypothermia.

Animals↗

PubMed2005

Effects of neuropeptide Y and corticotropin-releasing factor on ethanol intake in Wistar rats: interaction with chronic ethanol exposure.

Neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) have opposing effects on stress-associated and consummatory behaviors in rodents. Recent studies also suggest that both peptides influence ethanol intake. In the present study, the effects of administration of CRF and NPY into the lateral ventricle on ethanol intake in naive and ethanol-vapor-exposed Wistar rats were examined. A limited access paradigm was used to measure intake of a 10% (v/v) ethanol solution in Wistar rats trained to drink using a sucrose fading procedure. Ethanol vapor exposure for 8 weeks significantly elevated ethanol intake in this limited access paradigm relative to pre-exposure levels. The effects of icv administration of CRF (1 microg), NPY (10 microg) or NPY/CRF combined (10 and 1 microg, respectively) on ethanol intake were then assessed. In non-vapor-exposed subjects, icv infusion of NPY had no effect on ethanol intake, while a significant suppression of drinking was seen following icv administration of CRF. Administration of NPY in combination with CRF had no effect on ethanol intake in non-ethanol-vapor-exposed rats. In vapor-exposed subjects, both NPY and CRF reduced ethanol intake, but when given in combination, no difference from vehicle was detected. Locomotor activity was measured during drinking sessions and was unaffected by peptide administration. These studies underscore the importance of a history of exposure to chronic ethanol vapor in the regulation of ethanol intake by NPY. Furthermore, the results presented here suggest that a balance between the stress-related peptides NPY and CRF may be involved in the regulation of ethanol intake.

Alcohol Drinking↗

PubMed2003

Alcoholism and obesity: overlapping neuropeptide pathways?

Ethanol is a caloric compound, and ethanol drinking and food intake are both appetitive and consummatory behaviors. Furthermore, both ethanol and food have rewarding properties. It is therefore possible that overlapping central pathways are involved with uncontrolled eating and excessive ethanol consumption. A growing list of peptides has been shown to regulate food intake and/or energy homeostasis. Peptides such as the melanocortins, corticotropin releasing factor, and cholecystokinin promote reductions of food intake while others such as galanin and neuropeptide Y stimulate feeding. The present review highlights research aimed at determining if ingestive peptides also regulate voluntary ethanol intake, with an emphasis on the melanocortins and neuropeptide Y. It is suggested that research directed at ingestive peptides may expand our understanding of the neurobiological mechanisms that drive ethanol self-administration, and may reveal new therapeutic candidates for treating alcohol abuse and alcoholism.

Adrenocorticotropic Hormone↗

PubMed2005

The interoceptive cue properties of ghrelin generalize to cues produced by food deprivation.

A number of recent studies implicate the gut-brain peptide ghrelin as a putative "hunger signal". Most of these studies, however, rely on either consummatory behavior (in humans or nonhuman animals) or self-report (in humans) to draw conclusions regarding the orexigenic properties of this peptide. The present study employs the deprivation intensity discrimination paradigm to assess the interoceptive sensory properties of ghrelin in rats. In this paradigm, one group of rats was placed in a training context and presented with sucrose pellets when 24 h food deprived, but not when 1 h food deprived (24+ group). A second group was trained using the opposite sucrose-deprivation level contingency (1+ group). Learning in this paradigm was demonstrated by animals approaching the food delivery location more frequently under their rewarded compared to their non-rewarded deprivation condition (prior to actual pellet delivery). After asymptotic performance of this discrimination was achieved, these animals (1 h food deprived) were administered ghrelin or saline, either i.p. (3 or 6 nmol) or i3vt (0.1 or 1 nmol), placed in the training context, and appetitive responses were measured. Testing was conducted in extinction, eliminating confounding effects of food consumption. Results of these tests showed that 6 nmol i.p. ghrelin and 0.1 and 1 nmol i3vt ghrelin all generalized to a state of 24 h food deprivation, indicating that exogenous ghrelin has sensory properties in common with the stimuli produced by 24 h food deprivation. These results support the notion that endogenous ghrelin contributes to an interoceptive hunger cue, and that this may be a mechanism by which ghrelin influences food intake and appetitive behavior.

Animals↗

PubMed2006

Functional interaction between nociceptin/orphanin FQ and alpha-melanocyte-stimulating hormone in the regulation of feeding.

Nociceptin/orphanin FQ (N/OFQ), an endogenous agonist of the opioid N/OFQ (NOP) receptor, increases food intake when administered centrally. As N/OFQ is part of a larger neural network that governs consummatory behavior, presumably its orexigenic properties stem from interplay with other neuropeptidergic components of the feeding-related circuitry. One such peptide may be the ligand of the melanocortin-3 and -4 receptors, alpha-melanocyte-stimulating hormone (alpha-MSH), which is known to inhibit food intake. The aim of the present study was to establish whether there is a functional "interaction" between N/OFQ and alpha-MSH in the regulation of feeding. By using double immunostaining for c-Fos and alpha-MSH, we found that intracerebroventricular (i.c.v.) injection of N/OFQ at a 10nmol dose that moderately prolongs deprivation-induced food intake in rats, decreases activation of alpha-MSH neurons involved in feeding termination. However, i.c.v. injections of alpha-MSH at doses previously established to reduce deprivation-induced feeding, do not decrease hyperphagia generated by N/OFQ in ad libitum-fed animals. Our results suggest that while alpha-MSH does not appear to modify the orexigenic response to N/OFQ in sated rats, the NOP receptor ligand promotes a decrease in activation of neurons synthesizing the anorexigenic peptide, alpha-MSH, at the time of re-feeding. Thus, to some degree, the stimulatory effect of N/OFQ on consumption may arise from this peptide's inhibitory influence on activity of anorexigenic pathways containing alpha-MSH.

Animals↗

PubMed2001

Identification of central sites involved in butorphanol-induced feeding in rats.

Butorphanol (BT), a mixed kappa- and mu-opioid receptor agonist, induces vigorous food intake in rats. Peripheral injection of BT seems to increase food intake more effectively than intracerebroventricular administration. To further elucidate the nature of BT's influence on consummatory behavior, we examined which feeding-related brain areas exhibit increased c-Fos immunoreactivity (IR) following subcutaneous injection of 4 mg/kg body weight BT, a dose known to induce a maximal orexigenic response. We also evaluated whether direct administration of BT into the forebrain regions activated by peripheral BT injection affects food intake. Peripheral BT administration induced c-Fos-IR in the hypothalamic paraventricular nucleus (PVN), central nucleus of the amygdala (CeA), and nucleus of the solitary tract (NTS). However, 0.1-30 microg BT infused into the CeA, failed to increase food intake 1, 2, and 4 h after injection. Only the highest dose of BT (30 microg) injected into the PVN increased feeding. These results suggest that the PVN, CeA, and NTS mediate the effects of peripherally-injected BT. The PVN or CeA are probably not the main target sites of immediate BT action.

Amygdala↗

PubMed2001

Dietary soy phytoestrogens produce anxiolytic effects in the elevated plus-maze.

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets, exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body weight, consummatory behavior, and anxiety (as expressed in the elevated plus-maze). Phytoestrogens produced anxiolytic effects in both male and female Long-Evans rats. Additionally, phytoestrogens decreased body weight but increased consumption of food and/or water.

Androgens↗