Possible mechanism for the effect of anorexic agents on feeding and hoarding behaviour in rats

Amphetamine, fenfluramine, and chlorphentermine were tested for their effect on feeding and hoarding activity in rats, and the results interpreted according to a hypothalamic model for the regulation of motivated behaviour. All three compounds inhibited both feeding and hoarding, and the degree of inhibition was dose-dependent. Since feeding and hoarding are both influenced by activity in the lateral hypothalamus while feeding alone is modified by ventromedial hypothalamic activity, the result is consistent with a direct (inhibitory) action of the drugs on the lateral hypothalamus, rather than on the ventromedial region.     

Differential effects of morphine on food and water intake in food deprived and freely-feeding rats

In two experiments the effects of a range of doses of morphine (1, 3, 10 and 30 mg/kg) on the food and water consumption of rats were studied. The results of the first experiment showed that in 24 h food-deprived rats, morphine reduced levels of food and water intake. The duration of these actions was dependent upon dose, with only the highest dose (30 mg/kg) producing any effect persisting for longer than 4 h. In contrast a second experiment showed that morphine increased levels of food and water intake in non-deprived animals. The effect on food intake was most apparent when measurements were taken at 2 h and 4 h after drug administration, while water intake remained above control levels for over 6 h. This study shows that the actions of morphine on ingestion of food and water are affected by food deprivation, and the results are consistent with the hypothesised role of endogenous opiates in the mediation of such behaviour.     

Paradoxical effects of low doses of d-amphetamine in rats

Two experiments were conducted to examine the behavioral effects of low doses of d-amphetamine in rats. In contrast to previous studies showing depression of fixed-ratio 30 lever pressing by doses of d-amphetamine greater than 0.5 mg/kg, lower doses of the drug were found to facilitate such lever pressing. A low dose (0.05 mg/kg) of d-amphetamine was also found to enhance the amount of prandial drinking following food deprivation. These results indicated that the dose-response curve for d-amphetamine is generally non-monotonic and usually in the shape of an inverted U.     

Nicotine-induced conditioned place preference in adolescent rats

A number of clinical reports have noted that women are more vulnerable to tobacco abuse than men, and adolescent females are especially vulnerable to nicotine addiction. Conditioned place preference (CPP) is a widely used technique for determining the rewarding effects of drugs with abuse potential in animal models. Several studies have reported that nicotine was ineffective in eliciting CPP in rats; while others have observed conditioned place aversion (CPA) rather than preference for nicotine. One recent investigation established CPP in adolescent female rats, however at a reasonably high dose; while a second reported dose dependence of nicotine-induced CPP in male but not female rats. The present study was designed to determine the lowest dose necessary to induce CPP to nicotine in adolescent female rats. Nicotine-induced CPP was obtained at a subcutaneous dose of 0.03 mg/kg (salt content) using a biased conditioning paradigm. Higher doses produced aversion and lower doses provided no rewarding or aversive effects. CPP persisted for at least 3 weeks following conditioning in the absence of further nicotine treatment. In contrast with results from adolescent human females and males, age-matched male rats also evidenced CPP at this very low dose of nicotine. These results indicate that even a low dose of nicotine is reinforcing and addicting in both adolescent male and female rats and brings into question the suggestion that nicotine induces greater addicting capacity in adolescent girls than boys.     

Tolerance in the depression of intake when amphetamine is added to the rat's food

The depression of intake initially seen when a rat is placed on an amphetamine adulterated diet disappears over a week at the dose level of 0.2 mg amphetamine per gram of chow. The decreased effectiveness of amphetamine is attributable primarily to accruing deprivation rather than to either behavioral or pharmacological tolerance. Ventromedial hypothalamic lesions attenuate the tolerance, whereas lateral hypothalamic lesions decrease the basic anorexigenic effect of amphetamine.This work was partially supported by a NIGMS postdoctoral fellowship (1 FO 2 GM 44047-01) awarded to the first author and a MRC grant awarded to the second author.     

Effects of nicotine on body weight and food consumption in female rats

Women often report that they smoke cigarettes to avoid weight gains and that they relapse after abstaining from tobacco because of weight gains. Men also report these concerns but to a lesser extent. This gender difference may reflect sociological and cultural pressures about physical appearance, or it may reflect sex differences in the effects of nicotine. The present research was designed to examine the effects of nicotine administration and cessation of nicotine on body weight, food consumption, and water consumption. Alzet miniosmotic pumps were implanted SC to administer saline or three different concentrations of nicotine to female Sprague-Dawley rats for 17 days. This paradigm has been used in previous studies of nicotine and body weight in male rats. Animals were used as subjects to avoid cultural factors and cognitive concerns about body weight. Nicotine administration decreased normal body weight gains and cessation of nicotine was accompanied by significant increases in body weight compared to controls. In contrast to previous studies of male rats, the nicotine-related changes in body weight were accompanied by changes in bland food and water consumption. These findings indicate that females are more sensitive than males to the effects of nicotine on body weight and feeding during and after drug administration.     

Effects of nicotine on body weight and food consumption in rats

Recent human and animal studies have found that cigarette smoking or nicotine administration is accompanied by decreased consumption of sweet-tasting, high caloric foods. Cessation of smoking or nicotine is accompanied by increased consumption of these foods. Changes in consumption of these specific foods may partially account for the inverse relationship between smoking or nicotine and body weight. The present research was designed to determine whether consumption of nonsweet food is affected by nicotine and whether continuous access to only nonsweet foods attenuates the body weight changes associated with nicotine administration and cessation of nicotine administration. Alzet miniosmotic pumps were implanted SC to administer saline or three different concentrations of nicotine to male Sprague-Dawley albino rats for 2–3 weeks. Two studies on a total of 80 rats found an inverse dose-response relationship between nicotine administration and body weight without changes in bland food or water consumption. After cessation of nicotine administration, there were no differences in food consumption or body weight changes between groups. The effects of nicotine on body weight, both during and after drug administration, were attenuated in comparison to the results of studies that provided sweet-tasting foods.     

Nicotine-induced enhancements in the five-choice serial reaction time task in rats are strain-dependent

RATIONALE: Clinically, nicotine improves attention, but this has proven difficult to demonstrate preclinically. We tested nicotine in Sprague-Dawley (SD) and Lister hooded (LH) rats in the five-choice serial reaction time task. Since SD rats demonstrate lower asymptotic performance than LH rats, we surmised that nicotine would only improve performance in this strain. METHODS: Rats were placed in operant chambers 10 min after nicotine treatment (0.001-0.2 mg/kg). RESULTS: Nicotine dose-dependently increased correct responses only in SD rats (approximately 20% at the highest dose). By contrast, nicotine dose-dependently increased omission errors and reduced trials completed in both strains of rat, and dose-dependently reduced tray responses in SD rats. CONCLUSION: The magnitude of improvement in accuracy seen with nicotine in SD rats is greater than previously demonstrated using lesion or parametric manipulation models in other strains of rat in this test of attention. Although this suggests that the SD strain may be a useful "tool" for future studies, other task parameters, such as stimulus duration, may have to be optimum to demonstrate the magnitude of improvement observed presently.     

Nicotine-induced place preferences following prior nicotine exposure in rats

The motivational properties of morphine and nicotine were investigated in an automated conditioned place preference (CPP) procedure using a two-compartment apparatus. The accuracy of the photocell recording system was assessed by correlation with direct observation. In a counterbalanced conditioning design, graded doses of morphine (0.1–3.2 mg/kg SC) produced dose-related CPP. Under similar conditions, a dose of nicotine (0.6 mg/kg SC) previously reported to produce CPP failed to show an effect. Increasing the number of conditioning trials from 4 to 12 did not facilitate CPP with nicotine. After pretreatment with nicotine (0.4 mg/kg SC) daily for 7 days prior to conditioning, nicotine (0.4–0.8 mg/kg) produced increasing magnitudes of CPP. Locomotor activity was assessed during both conditioning and extinction tests. During conditioning, nicotine but not morphine decreased activity in the first conditioning trial, but by the fourth trial, marked stimulation was apparent following administration of either drug. Activity in the drug-paired compartment was not increased during tests for CPP carried out in the undrugged state following 4 conditioning trials with either morphine or nicotine, but there was evidence for conditioned hyperactivity after 12 conditioning trials with nicotine. The results suggest that motivational properties of nicotine can be detected in counterbalanced CPP procedures, but only in subjects with a history of nicotine exposure. The CPP produced by morphine or nicotine does not appear to be an artefact associated with conditioned changes in locomotor activity.     

Effects of heroin on lever pressing for intracranial self-stimulation,food and water in the rat

Male rats maintained with continuous access to levers for intracranial self-stimulation (ICSS), water, and food were subjected to five consecutive daily injections of heroin (5 mg/kg). Rates of lever pressing for ICSS were increased in 8 rats, 2–6 hrs after administration of heroin. Rates of lever pressing for water and food were not significantly changed during this period. Naloxone (5 mg/kg) pretreatment attenuated by 82% the facilitative effect of heroin on ICSS. A second group of 8 rats maintained at reduced ICSS rates failed to show an increase in lever pressing for ICSS with heroin. The facilitative effect of heroin described in this study is consistent with previously reported studies describing the effects of morphine on ICSS.     

Effects of nicotine on body weight in rats with access to “Junk” foods

The present experiment examined effects of nicotine on body weight of male and female rats when Oreo cookies, potato chips, laboratory chow, and water were available. Body weight and eating behavior were measured for 17-day periods before, during, and after nicotine or saline administration. There was an inverse relationship between nicotine and body weight. These effects were paralleled by changes in consumption of sweet foods. There were no effects of nicotine on salty or bland food consumption. Excessive gains in body weight after cessation of nicotine administration were greater for females than for males.     

Effects of the CCKB antagonist L-365, 260 on benzodiazepine withdrawal-induced hypophagia in rats

The effect of the selective CCK_B antagonist L-365, 260 on chlordiazepoxide (CDP) withdrawal-induced hypophagia was assessed in two related studies in rats pretreated for 21 days with CDP at doses escalated from 10 to 30 mg/kg per day (b.i.d.). L-365, 260 was studied at doses from 0.001 to 10 mg/kg (b.i.d.). There was no evidence that L-365, 260 at any dose alleviated CDP withdrawal-induced hypophagia. These data contrast with reports that CCK_B antagonists alleviate behavioural benzodiazepine (BZ) withdrawal symptoms considered to be indicative of anxiogenesis. Presumably, such positive effects of CCK_B antagonists are due to functional antagonism, with enhanced anxiety during BZ withdrawal being attenuated by anxiolytic actions of CCK_B antagonists. Collectively, studies with CCK_B antagonists and other agents involving a number of different BZ withdrawal signs suggest that BZ withdrawal is a heterogeneous syndrome, with various different underlying mechanisms. CCK_B antagonists appear to alleviate only a subset of possible BZ withdrawal signs.     

Sex differences in nicotine's effects on consummatory behavior and body weight in rats

Nicotine administration and cessation have greater effects on body weight and eating behavior in female than in male rats. These generalizations are based on studies of body weight and eating behavior for 2–3 week periods before, during, and after nicotine administration. Therefore, the sex differences may reflect differences in sensitivity to nicotine or simply differences in the time course of nicotine's effects. The present research was designed to replicate these previous studies and to examine long-term effects of nicotine cessation on body weight. Nicotine or saline was administered SC to female and male Sprague-Dawley rats for 16 days. Body weight, food consumption, and water consumption were measured before, during, and after nicotine administration. In addition, body weight was measured for 4 months after cessation of nicotine. There was an inverse relationship between nicotine and body weight. Also, there was an inverse relationship between nicotine and general consummatory behavior for females but not for males. The body weight of females that had received nicotine were indistinguishable from controls up to 4 months after cessation of nicotine. The body weight of males that had received 12 mg nicotine per kg per day remained lower than controls.This work was supported by the USUHS Protocol No. C07223. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense or the Uniformed Services University of the Health Sciences     

Use of phenylpropanolamine to reduce nicotine cessation induced weight gain in rats

The present study was conducted to determine if phenylpropanolamine (PPA) administered during the first week of nicotine termination could reduce or eliminate the body weight rebound which accompanies nicotine cessation. Sprague-Dawley rats were administered nicotine for 2 weeks after which they received either PPA or saline for 1 week. Control animals received saline during both drug periods. Body weight, food consumption, and water consumption were measured daily before drug, during nicotine and PPA administration, and for 14 days after PPA administration. In contrast to animals receiving saline upon termination of nicotine, animals receiving PPA did not gain weight at an accelerated rate. Termination of PPA did not result in a body weight rebound. To the extent that these results generalize to humans, they suggest that PPA could be used to reduce or eliminate postcessation weight gain in smokers who stop smoking.     

Nicotine-induced taste aversion: characterization and preexposure effects in rats

Rats were trained to drink their 24 hr water intake during a single daily 30 min period. After stabilization, rats were presented with 0.1% (w/v) of sodium saccharin for 30 min. Immediately after removal of the saccharin solution, the animals were injected with saline, mecamylamine hydrochloride or hexamethonium hydrobromide; thirty minutes later, saline or nicotine, 0.05, 0.16, or 0.50 mg/kg were administered. Twenty-four hr later, rats were allowed access to both water and saccharin. Nicotine caused a dose-related decrease in the proportion of fluid consumed as saccharin solution during the 30 min testing situation. Neither mecamylamine nor hexamethonium alone decreased saccharin preference; however, 3 mg/kg of mecamylamine blocked the decrease of saccharin preference induced by nicotine. Preexposure of drug-naive rats to 0.5 mg/kg of nicotine for 2 or 4 days abolished the nicotine-induced taste aversions to saccharin when tested one day, or one week, after conditioning.     

Effect of cocaine on food intake in rats

In rats trained to eat during a five-hour daily period, cocaine (10, 15, and 25 mg/kg) depressed food intake. The anorexia was seen during the 1st h only, with no effect on total food intake.This work was taken in part from a thesis submitted by DCB in 1976, in partial fulfillment of the requirements for the degree of Master of Arts, Dep't of Psychology, SUNY —Binghamton     

Amphetamine-induced hypodipsia and its implications for conditioned taste aversion in rats

According to the conditioned anorexia hypothesis, conditioned taste aversions occur when flavour stimuli are classically conditioned to the anorexigenic or hypodipsic effects of drugs. The effects on water intake of a range of doses of amphetamine and of several related compounds have therefore been examined in an attempt to correlate their known potentices in tate aversion experiments with their hypodipsic potencies (+)-Amphetamine was more potent than (-)-amphetamine in suppressing water intake but under similar experimental conditions, the isomers were equipotent in the conditioning of taste aversions. Methamphetamine and p-chloromethamphetamine were equipotent in suppressing water intake, but the latter was a more potent agent for conditioning taste aversions. Furthermore, fenfluramine produced taste aversions at doses well below those which suppressed water intake. It was concluded that the ability of the drugs to induce taste aversion was not related to their unconditioned, hypodipsic effects. However, it was confirmed that when drugs with different durations of action are compared for anorexic or hypodipsic potency, the outcome can be greatly influenced by the time over which measurements are made.     

Pharmacokinetic study of apomorphine-induced stereotypy in food deprived rats

The relationship between the effect of food deprivation on apomorphine-induced stereotypy and the plasma apomorphine concentration in rats was studied. Male Wistar rats, allowed to have free access to food and water or deprived of food for 48 hr, were injected subcutaneously with apomorphine hydrochloride (10 mg/kg). Food deprivation was liable to potentiate the apomorphine-induced stereotypy in the early stage after dosing. Higher plasma apomorphine concentrations were found in the food deprived rats at this observation period. The potentiation of apomorphine-induced stereotypy following food deprivation can in part be explained by the pharmacokinetic changes. The exact mechanism of the effect of food deprivation on apomorphine kinetics is not clear at present.     

Effects of methamphetamine on fixed-ratio responding of food satiated and food deprived rats

After the initial training of the lever pressing response for sweetened condensed milk, rats were put on different fixed-ratio (FR) schedules of reinforcement under conditions of being food satiated and food deprived. Doses of methamphetamine ranging from 0.125 to 1.0 mg/kg were tested in these rats for effects on response rates. Response rates of the satiated rats at the higher FR requirements were slower than those of the deprived rats. At the doses of methamphetamine used, the satiated animals responded at slower than their control response rates and the deprived rats tended to respond faster than control rates.     

Nicotine-induced conditioned place preference in rats: Sex differences and the role of mGluR5 receptors

To elucidate sex differences in nicotine addiction and the underlying mechanisms of the conditioning aspects of nicotine, nicotine-induced conditioned place preference (CPP) was evaluated in male and female Sprague Dawley rats using a three-chambered CPP apparatus and a biased design. In a series of experiments, the dose-response curve was obtained, pairings between the drug and initially non-preferred versus preferred compartments were compared, and the involvement of mGluR5 receptors in nicotine-induced CPP was evaluated. Modulation of nicotine-induced CPP with mGluR5 inhibition was obtained by MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride). Our results show that nicotine induces CPP dose-dependently in male rats but not in female rats. The comparison of the biased protocol, pairing nicotine with the initially preferred and non-preferred chambers, indicated that nicotine-induced CPP in male rats under both conditions, but the effect was stronger when nicotine was paired with the initially non-preferred side. The selective mGluR5 antagonist MPEP inhibited nicotine-induced CPP in male rats. In conclusion, the results of the current study in rats demonstrate that the conditioning effect of nicotine is more important in males than in females. Furthermore, in line with reported findings, our results suggest that mGluR5 antagonism may be therapeutically useful in smoking cessation during the maintenance of smoking behavior when conditioning plays an important role, notwithstanding the fact that this effect is observed only in male rats, not in females.