Effects of chronic amitriptyline and desipramine on food intake and body weight in rats

Long-term treatment with tricyclic antidepressant drugs (TCAs) can induce excessive body weight gain in a significant proportion of patients. Such weight gains, which appear to be largely independent of clinical improvement, are in many cases severe enough to interfere with continuation of treatment. In efforts to model this effect in experimental animals, seven experiments were performed in which two commonly used TCAs, amitriptyline and desipramine, were administered chronically to rats. Despite manipulations of drug dosages (2.5 mg-17 mg/kg), route of administration (intraperitoneal, subcutaneous, oral; daily injections vs. continuous release from osmotic pumps), diet composition and palatability (regular Purina Chow pellets or powder with or without added high fat and high carbohydrate sources; high vs. low protein diets) and animal sex and housing conditions (single vs. group housing), chronic TCA treatment was never observed to increase daily food intake or rates of body weight gain. Desipramine treatment invariably caused decreased food intake and weight loss. Amitriptyline treatment either caused no change in food intake and body weight or slightly reduced levels in comparison to vehicle-treated controls. However, both amitriptyline- and desipramine-treated rats showed a potentiation of acute caloric intake after a single systemic injection of the glucoprivic agent 2-deoxy-D-glucose. These results are considered against the background of human clinical observations. Possible reasons for the differences between human and animal data are discussed.     

Effects of naltrexone on food intake and body weight gain in olanzapine-treated rats

Blockade of opioidergic neurotransmission contributes to reduction in body weight. However, how such blockade affects body weight gain (BWG) attributed to second generation antipsychotic agents (SGAs) has not yet been established. Here we examined the effects of an opioid receptor antagonist, naltrexone (NTX), on food intake and BWG associated with an SGA, olanzapine (OL). Four groups of Wistar Han IGS rats were treated for 28 days with either OL (2 mg/kg twice daily, intraperitoneal (IP)), a combination of OL (2 mg/kg twice daily, IP) + extended-release NTX (50 mg/kg, one-time, intramuscular (IM)), extended-release NTX (50 mg/kg, one-time, IM) or vehicle and their food intake and body weight were measured daily for the first nine days and every other day thereafter. Food intake and BWG that were increased by OL were decreased by the added NTX while NTX alone had no significant effects on food intake or on BWG. Plasma leptin concentrations were significantly elevated in the three groups receiving pharmacological agents, but did not differ among each other, suggesting that changes in leptin secretion and/or clearance alone would not explain the food intake and the body weight findings. Our results extend prior reports on anorexigenic effects of opioid antagonists by demonstrating that such effects may generalize to food intake increases and BWG arising in the context of OL pharmacotherapy.     

Effects of acarbose on food intake,body weight and fat depots in lean and obese rats

Effects of dietary acarbose at 0, 5, 15 and 50 mg per 100 g diet on food intake and body weight were studied for two months in female rats. The relationships between diet composition, the drug dose and the type of obesity were examined. In lean rats receiving the drug in a high carbohydrate diet (70 Cal.%), mean food intake was similar to control at 5 and 15 mg dietary levels, but was significantly increased at 50 mg. Body weight was significantly reduced only at the 15 mg level. In VMH obese rats receiving the drug in a high carbohydrate diet, it resulted in significant reductions in food intake at the 15 and 50 mg drug levels and in significant reductions in body weight at all three drug levels. In dietary obese rats receiving the drug in a high carbohydrate diet and also in a 32% sucrose drinking solution, food intake and body weight were significantly reduced at each of the drug levels. In dietary obese rats receiving the drug in a high fat diet (70 Cal.%), acarbose at all levels resulted in only small and usually not significant changes in either food intake or body weight. Weight of fat depots were significantly reduced at the 50 mg dietary level in all instances where a high carbohydrate diet was used while at the 5 mg level, fat depots were reduced only in the VMH obese, with the sucrose obese showing a trend for reduced depots. Acarbose in the high fat diet resulted in no significant changes in weight of fat depots. These data indicate that acarbose in a high carbohydrate diet is effective in reducing weight of rats, and that obese usually show a greater reduction in food intake and body weight than lean rats.     

Effects of alcohol on cocaine lethality in rats: acute and chronic assessments

Cocaine and alcohol is a popular, yet toxic, drug combination that results in effects greater than that of either drug alone. The following experiment presents additional evidence that supports this position. Specifically, the lethal effects of acute (1 day) and chronic (4 days) alcohol (0.5 g/kg), cocaine (20, 30, or 40 mg/kg), or the respective alcohol/cocaine combinations were assessed in rats. For acute drug administration, lethality was only evident in those animals administered the combination of 0.5 g/kg alcohol and 40 mg/kg cocaine, supporting the position that the effects of combining alcohol and cocaine are greater than either drug alone. Chronic drug administration resulted in a weak sensitization to cocaine-induced lethality that was increased when alcohol was combined with cocaine. Together, this evidence suggests that combining alcohol and cocaine (acutely) can have lethal consequences in rats that are greater than either drug alone, effects that can be exacerbated with chronic use.     

Effect of chronic treatment with clomipramine on food intake, macronutrient selection and body weight gain in rats

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; 16th-18th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.     

The effects of chronic treatment with fencamfamine on body weight, food intake and stereotyped behaviour in rats

The effects of chronic treatment with fencamfamine (10.0 mg/kg, i.p.) or saline were studied in rats. Chronic fencamfamine treatment reduced body weight of rats below their normal body weight. Thereafter, weight increased, in parallel to that of control rats. There was an increasing trend in food intake in both groups and a reduction was observed in food intake on the first seven days of fencamfamine-treated rats. Fencamfamine repeated administration enhanced stereotyped sniffing while rearing behaviour gradually declined until 25 days. However, the same treatment did not interfere with the intensity of stereotypy. These findings suggest the need for a re-evaluation of current concept in the tolerance to the effects of fencamfamine and other stimulant drugs.     

The effects of chronic nicotine on meal patterns, food intake, metabolism and body weight of male rats

It is unclear what contribution food intake and metabolism have in causing weight loss after administering a dose of nicotine equivalent to smoking one to three packs of cigarettes per day because previous studies have been of a very short duration. To address this question, male Sprague Dawley rats were housed in computerized food intake modules and fed 45 mg pellets: Group 1 [nicotine injected with 1.4 mg/kg/day (free base), fed ad libitum]; and Group 2 [saline injected and pair-fed by computer with Group 2]; and Group 3 [saline injected (i.p.), fed ad libitum]. The rats received 4 equally spaced injections over the dark phase. Treatment consisted of: Phase 1 (nicotine or saline for 14 days), Phase 2 (all rats saline for 8 days and Phase 3 (pair-fed group “unyoked” for 6 days)). Nicotine inhibited food intake over the first 6 days. On termination of nicotine, there was no compensatory hyperphagia in either Groups 1 or 2; and their body weight was reduced starting on day 5 until day 28. In another study, rats were housed in an indirect calorimetry system. Saline or nicotine was injected for 14 days, as noted above; then all rats were injected with saline for 4 days and then no injections for 10 days to follow changes in body weight. Energy expenditure (Kcal/Kg^0.75) was measured for 18 days. Nicotine significantly reduced food intake on 7 of 14 days of nicotine injections. The body weight of the nicotine injected rats was significantly reduced starting on day 3 until day 25. There were no differences in energy expenditures of the groups, which suggested that a decrease in food intake and not an increase in metabolism was the reason the rats lost weight after administering nicotine.     

Effects of acute and chronic ethanol intake on synaptosomal glutamate binding activity

The effects of acute and chronic ethanol administration in vivo, on brain synaptosomal glutamate binding activity were explored. In the l-glutamic acid concentration range in which high affinity stereospecific binding to synaptic membranes takes place, both acute and chronic ethanol administration led to progressively greater glutamate binding depending on the chronicity of exposure to ethanol (2 hr to 16 days). These changes appeared to be primarily due to an increase in the maximum binding capacity of these membrane binding sites rather than to changes in their affinity towards the ligand. The withdrawal from ethanol following 16 days of continuous exposure brought about a slow reversal of the increased glutamate-binding activity over a period of 6 days. A brief (2 hr) exposure to ethanol in vitro, produced a small decrease in glutamate binding, whereas prolonged exposure to the alcohol during equilibrium dialysis had a biphasic effect on ligand binding to synaptosomal membranes. These results are suggestive of a possible role for l-glutamic acid in the nervous system during ethanolism and the post-withdrawal reaction.     

Effects of body weight reduction and food deprivation on cocaine self-administration

The present experiments attempted to study the effects of food deprivation and body weight reduction on cocaine self-administration. Rats whose body weight was reduced to 80% free feeding weight (FFW) with 23 hours' food deprivation increased cocaine intake by 30-fold compared to 100% FFW animals. The results demonstrated that, in rats, body weight reduction and the state of food deprivation interact to further enhance self-administration of cocaine. From the practical point of view, the results suggest that there may be an increased risk of drug dependence with patients taking stimulants to control body weight.     

Effects of thiamine deficiency on food intake and body weight increment in adult female and growing rats

The present study compared the effects of thiamine (vitamin B1) deficiency (TD) on the patterns of food intake and body weight in adult female and neonatal Wistar rats. The adults weighed 250-270 g at the start and were fed for 60 days either with a synthetic TD diet (211 B1) or with the same synthetic diet+thiamine (210 B1). TD led to a marked reduction in food intake and the body weight set point, both recovering rapidly to their initial level in only 3 days after dietetic reversion. The effects of TD in developing rats were evaluated by subjecting pregnant rats to thiamine restriction during different time windows: prenatal (3 days before mating to parturition); perinatal (7 days after mating to the 10th postnatal day); and postnatal (from parturition to weaning). The effect of TD on the occurrence of low birth weight and ponderal growth retardation was examined from postnatal days 1 to 45. Only perinatal TD significantly decreased birth weight relative to untreated or pair-fed controls. Moreover, compared with the control treatments, ponderal growth retardation was not induced by prenatal TD, whereas induction of TD from perinatal into postnatal periods did cause ponderal growth retardation, with long-lasting effects persisting in adulthood. The results suggest a major physiological role of thiamine in the homeostasis of body weight programming, increment, and set point regulation in both offspring and adult female rats.     

Effects of chronic phenylpropanolamine infusion and termination on body weight,food consumption and water consumption in rats

The present study determined the effect of chronic PPA infusion and withdrawal on weight regulation. Male Sprague-Dawley rats received PPA (0, 90 or 180 mg/kg) via miniosmotic pumps for 2 weeks. Body weight and food and water consumption were measured daily before, during, and for 2 weeks after PPA infusion. Additionally, body weight was measured once 6 weeks after the last day of drug administration. PPA infusion produced dose-dependent reductions in body weight and food consumption throughout drug administration. During the first week of PPA termination, food consumption returned to control levels; however, body weights of drug-treated animals remained below those of controls throughout the 6-week post-drug period. PPA depressed water intake during the first week of drug administration, but tolerance to this effect developed by the second week of administration. These results suggest chronic PPA infusion produces persistent appetite suppression and weight loss and that discontinuation of PPA does not result in hyperphagia or rapid weight gain. These findings may have clinical significance for the many individuals who wish to lose weight but have difficulty reducing intake without pharmacologic assistance.     

Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats

1. The aim of the study was to compare the effects of 14 day subcutaneous infusion of the 5-HT(2C) receptor agonists, m-chlorophenylpiperazine (mCPP, 12 mg kg(-1) day(-1)) and Ro 60-0175 (36 mg kg(-1) day(-1)) and the 5-HT releasing agent and re-uptake inhibitor, d-fenfluramine (6 mg kg(-1) day(-1)), on food and water intake, body weight gain and locomotion in lean male Lister hooded rats. 2. Chronic infusion of all three drugs significantly reduced food intake and attenuated body weight gain. In contrast, drug infusion did not lead to significant reductions in locomotor activity in animals assessed 2 and 13 days after pump implantation. 3. In a subsequent 14 day study that was designed to identify possible tolerance during days 7 - 14, animals were given a subcutaneous infusion of mCPP (12 mg kg(-1) day(-1)) or d-fenfluramine (6 mg kg(-1) day(-1)) for either 7 or 14 days. During the first 7 days both drugs significantly reduced body weight gain compared to saline-infused controls; however, from day 7 onwards animals withdrawn from drug treatment exhibited an increase in body weight such that by day 14 they were significantly heavier than their 14-day drug-treated counterparts. 4. Both mCPP and d-fenfluramine reduced daily food intake throughout the infusion periods. For 14-day treated animals this hypophagia was marked during the initial week of the study but only minor during the second week. In light of the sustained drug effect on body weight, the data suggest that weight loss by 5-HT(2C) receptor stimulation may be only partly dependent on changes in food consumption and that 5-HT(2C) receptor agonists may have effects on thermogenesis. 5. These data suggest tolerance does not develop to the effects of d-fenfluramine, mCPP and Ro 60-0175 on rat body weight gain.     

Effects of marihuana use on body weight and caloric intake in humans

Body weight and caloric intake were measured in a group of heavy and casual marihuana users prior to, during and following 21 days of marihuana smoking under research ward conditions. A group of control subjects were studied under identical conditions, but they did not smoke marihuana. Both heavy and casual marihuana users had a significant increase in caloric intake and gained weight during the marihuana smoking period. Heavy and casual users gained an average of 3.7 and 2.8 lbs respectively during the first 5 days of marihuana smoking. In contrast, control subjects gained only a small amount of weight (0.2 lbs) during the same time interval. Water retention did not appear to be a major factor in weight gain by the marihuana users. These findings are in agreement with both anecdotal reports and previous experimental data that marihuana use is associated with increased caloric intake and weight gain.     

Effects of ovariectomy and estradiol injections on food intake and body weight in rats with ventromedial hypothalamic lesions

Female rats with lesions of the ventromedial hypothalamus (VMH) were ovariectomized during the static obese stage efter body weight levels had stabilized. Following ovariectomy, rats with VMH lesions showed smaller increases in food intake and less body weight gain than non-lesioned controls ovariectomized at the same time. Subsequently, the effects of peripheral injections of estradiol benzoate (EB) on feeding and body weight were examined. Ovariectomized rats with VMH lesions were also less responsive to exogenous EB treatment; they lost significantly less weight in response to estrogen than controls. EB caused a somewhat smaller reduction in food intake by the VMH group but this difference was not significant. Considered together the available data on changes in responsiveness to endogenous and exogenous estrogen following VMH lesions suggests a role for VMH estrogen receptors in the regulation of body weight, but these estrogen receptors may not modulate weight by directly altering food intake as previously suggested.     

Effects of nicotine on body weight, food intake and brown adipose tissue thermogenesis

Chronic treatment with nicotine results in reduced body weight gain without a change in food intake. To evaluate the role of brown adipose tissue (BAT) thermogenesis in this effect of nicotine, male Sprague-Dawley rats were chronically treated (3X daily, IP) over a 14 day period with either saline, 0.8 mg/kg nicotine, 10 mg/kg caffeine or a combination of 0.8 mg/kg nicotine and 10 mg/kg caffeine and were pretreated (once daily) with either saline or 20 mg/kg nadolol, a long-acting beta-adrenergic receptor blocker. Nicotine significantly reduced body weight gain but not food intake and nadolol did not reverse the effect of nicotine on body weight gain. To evaluate whether nicotine induces BAT thermogenesis, rats were injected IP with either saline or 0.8, 1.2 or 1.6 mg/kg nicotine hydrogen tartrate, with 5 mg/kg dl-phenylpropanolamine (dl-PPA) or with a combination of 0.8 mg/kg nicotine and 10 mg/kg caffeine with interscapular BAT (IBAT) temperatures recorded for 30 minutes after injection. No dose of nicotine produced a change in IBAT temperature whereas a combination of caffeine and nicotine produced a temperature increase in IBAT (0.95 degree C) 63% of that induced by 5 mg/kg dl-PPA. These data suggest that changes in body weight gain induced by nicotine treatment are not the result of an action of nicotine on BAT thermogenesis.     

Self-administration of low-dose cocaine by rats at reduced and recovered body weight

Food deprivation significantly increases self-administration of cocaine in both rats and rhesus monkeys. The objective in the present investigation was to determine the effects of varying deprivational states on the level of IV low-dose (0.1 mg/kg/infusion) cocaine self-administration in rats. In the first experiment, 32 naive rats were assigned randomly to four equal-sized groups. Two groups self-administered cocaine, the other two saline over two consecutive 10-day phases. Across phase 1 all animals were free-feeding (FF), while in phase 2, one cocaine- and one saline-reinforced group were subjected to restricted feeding until they reached 80% free-feeding weight (FFW). Results showed that cocaine-reinforced responding was related inversely to body weight. In experiment 2 another 32 rats, reduced to 80% FFW, were assigned to four equal-sized groups. Two groups self-administered cocaine, the other two saline over two consecutive 10-day phases. Across phase 1 all animals were maintained at 80% FFW, while in phase 2, one cocaine- and one saline-reinforced group were abruptly food satiated. Findings showed that cocaine-reinforced responding decreased rapidly to low levels. Finally, the group of cocaine-reinforced rats maintained at 80% FFW across both phases of experiment 2 were also abruptly food satiated. Again, responding decreased rapidly to low levels.     

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     

Effects of injection of serotonin into nucleus caudatus on food and water intake and body weight in albino rats

Serotonin is known to inhibit food and water intake. However, the effect of its injection into nucleus caudatus on food and water intake is not known. In the present study, serotonin hydrochloride, buspirone (the serotonin 5-HT1A agonist) and ondensetron (the 5HT3 antagonist) were injected into nucleus caudatus through stereotaxically implanted cannulae in three different dosages (1, 2 and 5 microg) and their effects on 24 h food and water intake, and body weight were recorded. The injection of serotonin hydrochloride resulted in a dose- dependent decrease in food intake attaining maximum of 27.3% at 5 microg dose, whereas water intake and body weight were decreased 12% and 4.3% respectively only at the highest does. Buspirone elicited a dose dependent inhibition of food and water intake and body weight (22.3%, 19.8% and 5.1% respectively), whereas ondensetron elicited an increase in food and water intake (37.8% and 36.3% respectively) without significantly altering bodyweight. It was concluded that serotonin hydrochloride injected into nucleus caudatus inhibits food and water intake significantly. These effects are mediated via 5-HT1A and 5HT3 receptors. The effect of injections of 5-HT1A receptor agonist is more pronounced on water intake. The effect of injections of 5HT3 receptor antagonist is also more pronounced on water intake.