The effects of putative anxiogenic compounds (FG 7142, CGS 8216 and Ro 15-1788) on the rat corticosterone response

The effects of FG 7142, CGS 8216 and Ro 15-1788, three compounds that are believed to produce anxiety by an action at benzodiazepine receptors in the CNS, are investigated on the plasma corticosterone concentrations in the rat both in the home cage and after exposure to novelty stress. FG 7142 (5 mg/kg) and CGS 8216 (10 mg/kg), but not Ro 15-1788 (4 or 10 mg/kg) increased basal corticosterone levels in the home cage, and all three compounds potentiated the increase in corticosterone concentrations observed after exposure to a novel environment. The relationship between the effects of drugs on corticosterone concentrations and on anxiety is considered in the light of these results.     

Flavor,forced choice and deprivation affect corticosterone selection by the adrenalectomized rat

Adrenalectomized rats were given access to corticosterone-supplemented (20 μg/ml) and-unsupplemented saline (0.9% NaCl) in two separate bottles and preferences were measured for each. Half of the rats received corticosterone in maple-flavored saline (MAPLE group), while the other half received corticosterone in anise-flavored saline (ANISE group). Each rat also received unsupplemented saline in the alternate flavor. After an initial preference test, preferences were measured again following a period of forced choice (where rats were given the supplemented saline only) and again following a period of deprivation (where rats were given the unsupplemented saline only). All three independent variables (flavor, forced-choice and deprivation) played roles in determining self-administration of corticosterone. Results from the initial preference test demonstrated that both groups preferred the maple-flavored saline whether it contained corticosterone or not. However, consumption of corticosterone-supplemented saline regardless of flavor increased following both forced-choice and deprivation suggesting that the adrenalectomized rats were controlling their corticosterone levels. Strong negative correlations were found between intake of corticosterone-supplemented saline and body weight suggesting that the adrenalectomized rat may be controlling corticosterone levels based on some correlate of body weight.     

Schedule-induced drinking and other behavior in the rat, as a function of body weight deficit

Six rats were presented with food according to a fixed time 60-sec schedule at 80%, 90% and 100% of their initial ad lib body weight, and with food freely available in the home cage. Water was available at all times. Amount of water consumed during test sessions, time spent drinking, number of bouts of drinking, and bout duration of drinking varied inversely with body weight. Visiting the food tray also varied inversely with body weight, while grooming varied directly. In rats fed ad lib in their home cages, more water was drunk when pellets were intermittently scheduled than when the same number of pellets was freely available in a session of equal duration, but time spent grooming did not vary significantly. Thus, drinking is schedule-induced in satiated rats, but grooming is not. It is suggested that the primary effect of satiation is to reduce drinking, and that grooming increases secondarily to fill the time vacated by drinking.     

Cannabidiol decreases body weight gain in rats: involvement of CB2 receptors

Cannabidiol (CBD) is a major non-psychotropic constituent of Cannabis sativa, with well recognized therapeutic potential. Considering the importance of the endogenous cannabinoid system to the regulation of food intake and energy balance we studied the effects of repeated CBD administration on body weight gains in rats. Male Wistar rats (260 ± 20 g at start of study) received intraperitoneal injections of CBD at doses of 2.5 and 5mg/kg/day for 14 consecutive days and body weight gains were monitored. Both doses of CBD produced significant decrease in body weight gain, with the effect produced by 5mg/kg being more pronounced. The CB2 receptor selective antagonist, AM630, blocked the decrease in body weight gain. AM630 alone did not affect body weight gain. The results suggest that CBD has the ability to alter body weight gain, possibly via the CB2 receptor. CB2 receptors may play a role in the regulation of body weight and the effects of CB2 specific ligands should be further investigated in studies of body weight regulation.     

Relation between estrogen-induced hyperlipemia and food intake and body weight in rats

Thirteen experiments on 348 ovariectomized female rats examined the relationship between estradiol's effects on food intake and body weight and on plasma triglycerides, free glycerol, and fatty acids. The time course of estradiol benzoate effects on food intake and weight gain differed from the time course of triglyceride elevation. The antiestrogen, nafoxidine, given with estradiol blocked the hypertriglyceridemia, but not the weight loss, resulting from estradiol benzoate. Estradiol benzoate treatment for up to three days had no significant effect on plasma triglyceride levels following intragastric and intravenous triglyceride administration. Changes in plasma triglyceride following Triton WR-1339 indicated that the absolute rates of plasma triglyceride clearance were not impaired by estradiol. These results contradict Wade and Gray's [31] hypothesis about the mechanism of estradiol-induced hypophagia.     

Effects of stereoisomers of estradiol on food intake, body weight and hoarding behavior in female rats

The effects of 17-alpha and 17-beta estradiol on food intake, body weight and hoarding behavior in ovariectomised rats were investigated. For five days, ten animals received subcutaneous injections of both isomers (10 micrograms/kg/day) in a counterbalanced design. Hoarding tests were conducted on the last three days of each 5-day injection period. 17-Alpha estradiol significantly reduced food intake but was without effect on body weight. 17-Beta estradiol reduced food intake significantly more than the alpha form and also significantly reduced body weight. These differential effects suggest that stereoisomers of estradiol may be acting on separate regulatory systems. The treatments did not change hoarding activity compared to pre-treatment levels.     

Salicylate as a partial inhibitor of emotional fever and body weight set-point in rats: behavioral and neuroendocrine study

In this article, we report findings from behavioral and neuroendocrine experiments in rats under pharmacologically induced antipyretic conditions. Endpoints included emotional fever, body weight setpoint, and in situ corticotropin-releasing hormone mRNA (CRHmRNA) expression. Nine male Wistar rats were treated with acetylsalicylic acid (ASA) 0.04 g/kg ip in vehicle. On alternating days, all rats received saline (0.9% w/v) as a control. ASA was selected chiefly for its antipyretic and also for effects on metabolism. It has been demonstrated that gentle handling affects body weight and body temperature in rats. In Experiment 1, we investigated whether blocking emotional fever by ASA treatment would inhibit the lowering of the body weight setpoint induced by handling of the rats. Rats were exposed to a daily food-hoarding session under handling stress, and their body weight setpoints were calculated from the hoarding measurements. As rats received ASA and saline in an alternating manner, two setpoints were calculated. In Experiment 2, we performed neuroendocrine analyses of CRHmRNA expression in the same group of animals from Experiment 1. CRHmRNA was determined by in situ hybridization. Results indicated that ASA treatment in rats significantly decreased the body weight setpoint (P=.02) and significantly prevented increases in body temperature due to emotional fever (P=.03) when compared to their control values. Findings also revealed that hypothalamic CRH expression was increased when rats were treated with ASA. ASA did partially block fever induced by handling, but it is difficult to confirm whether emotion was also inhibited by treatment. Taken together, these results indicate that salicylates affect energy balance and might be a good inhibitor of body weight gain in rats.     

Ovarian influences on food intake and body weight regulation in lactating rats

In the following experiments, an attempt was made to determine the role of the ovary in the control of food intake and body weight regulation during lactation. In the first study, it was found that concentrations of estradiol benzoate effective in suppressing food intake and body weight in nonlactating animals were not effective during lactation. In the second experiment, ovariectomy during lactation was shown not to produce the usual increases in food intake and body weight or change in meal patterns known to occur after ovariectomy in the nonlactating rat. These results suggested that lactating animals behave the as though functionally ovariectomized and that the removal of the ovaries is of no additional consequence. The further observation that animals nursing small litters gained weight considerably more rapidly than animals nursing large litters led to the prediction that these animals would also be more responsive to the suppressive effects of EB. In the third study, EB in concentrations which are not effective in suppressing body weight in animals nursing large litters was found to suppress body weight in mothers with small litters. However, since these animals also showed a decline in milk yield, a number of alternative interpretations of these results were considered. These results, together with data concerning levels of ovarian hormones during gestation and lactation led to the hypothesis that pregnant and lactating animals undergo an elevation in body weight set-point, similar in magnitude and quality to elevations following ovariectomy in the nonlactating animal.     

Sex differences in the effects of dexamethasone phosphate on behavior in rats.

The effect of dexamethasone phosphate (DEX) administered in rats' drinking water on running activity and open field behavior was investigated. In Experiment 1 males were given DEX continuously from either five days or one day prior to and throughout testing. Only 5 day treatment significantly increased running wheel activity. DEX had no significant effect on males' 4 day open field activity, but significantly reduced open field and home cage defecation. In Experiment 2 females given DEX defecated significantly more in the open field than controls. This effect on females does not appear to be due to a general metabolic change, since DEX females, like males, defecated significantly less than controls in the home cage. Females' open field activity was not significantly affected. Weight loss and plasma corticosterone analysis confirmed the effectiveness of the dosage used. There appears to be a sex difference in the effects of DEX on open field defecation, possibly due to interaction with gonadal hormones.     

The effects of estradiol on body weight and food intake in normal weight VMH-lesioned rats.

The effects of estradiol on food intake and body weight were examined in ovariectomized and VMH-lesioned, ovariectomized rats that were prevented from supranormal weight gain by food restriction. Estradiol injections that were effective in reducing weight in supranormal weight, ovariectomized rats had no effect on weight in normal weight, ovariectomized or VMH-lesioned, ovariectomized rats. Estradiol did not prevent hyperphagia and weight gain in VMH-lesioned, ovariectomized rats when they were provided with ad lib food.     

Sexual dimorphism in passive avoidance behavior of rats: Relation to body weight,age, shock intensity and retention interval

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.     

Copulation affects body weight but not food intake or dietary self-selection in male rats

The mechanisms responsible for copulation-induced changes in body weight were investigated using adult male rats. Animals that copulated two or three times a week for 6 weeks gained less weight than sexually inactive controls. The reductions in body weight gain were not associated with changes in total caloric intake or the intake of specific nutrients. Adipose tissue lipoprotein lipase activity was not affected by sexual activity. Based upon these results and previous observations, we suggest that copulation-induced reductions in body weight may not be mediated solely by testicular testosterone.     

Melatonin and estradiol effects on food intake, body weight, and leptin in ovariectomized rats

OBJECTIVE: The study in ovariectomized (Ovx) rats, as a model of menopausal status, of the effects of melatonin (M) and/or estradiol (E), associated or not with food restriction, on body weight (BW) and serum leptin levels. METHODS: Female SD rats (200-250 g) were Ovx and treated with E, M, E+M or its diluents. Control sham-Ovx rats were treated with E-M diluents. After 7 weeks being fed ad libitum, the animals were exposed for 7 more weeks to a 30% food restriction. We measured: food intake, BW, nocturnal and diurnal urinary excretion of sulphatoxymelatonin (aMT6s), leptin in midday and midnight blood samples, glucose, total cholesterol, LDL, HDL and triglycerides. RESULTS: Day/night rhythm of aMT6s excretion was preserved in all cases. The increase of aMT6s excretion in M-treated animals basically affected the nocturnal period. In animals fed ad libitum, E fully prevented Ovx-induced increase of BW, leptin and cholesterol. Melatonin reduced food intake and partially prevented the increase of BW and cholesterol, without changing leptin levels. Under food restriction, M was the most effective treatment in reducing BW and cholesterol. Leptin levels were similar in M, E or E+M treated rats, and lower than in untreated Ovx rats. CONCLUSIONS: Our result gives a preliminary experimental basis for a post-menopausal co-treatment with estradiol and melatonin. It could combine the effectiveness of estradiol (not modified by melatonin) with the positive effects of melatonin (improvement of sleep quality, prevention of breast cancer, etc.). The possible beneficial effects of melatonin which could justify its use, need to be demonstrated in clinical trials.     

Changes in actual versus defended body weight elicited by a varied, palatable ("supermarket") diet in rats

Male rats fed on a varied, palatable supermarket diet for 11 weeks gained more weight than chow-fed controls. When palatable food was discontinued, their body weights became static, but remained significantly higher than control weights for a further 5 weeks. Hoarding of food was readily elicited by food deprivation in the dietarily obese as well as in the chow-fed rats. Previous studies have shown that the critical body weight at which hoarding appears does not covary with body weight, but appears to reflect a defended level of body weight. In the present study, critical weights were not significantly different between groups before supermarket diet, but were significantly higher in the supermarket rats after obesity had developed. Thus, the increase in body weight brought about by a supermarket diet (unlike that in ventromedial hypothalamic obesity) can be accompanied by an increase in the defended level of body weight as inferred from the critical weight for the onset of hoarding behaviour.     

Relationship between wheel running, feeding, drinking, and body weight in male rats

The amount of wheel running varies widely between rats. Wheel introduction and running also have profound effects on the animal's energy balance. We explored the effects of ad lib wheel access and running levels on feeding, drinking, and body weight in 30 young adult male rats with wheel access and in 30 rats without wheel access. The initial running period (Days 1-8) and a time of stable running [Days 29-32 (DEnd)] were analyzed using both between- and within-group approaches. Initially, wheel access suppressed feeding (by about 25% over the 8 days) but not drinking. There were no significant correlations between the amount of wheel running and the other behaviors. The degree of feeding suppression was also not correlated to the amount of running. When running had stabilized (animal ran from 841 to 13,124 wheel turns per day), food intake was increased by about 0.75 g per 1000 wheel turns. Running at this time correlated positively with feeding and drinking and negatively with body weight and weight gain. In animals without wheel access, feeding and drinking were positively correlated with weight and weight gain, but in animals with wheel access, these correlations were close to zero. Only early running predicted later levels of running but accounted for only 23% of the variance in running. Wheel access has profound but very different immediate and long-term effects on the rats' energy balance.     

Food intake and body weight modifications following medial hypothalamic hormone implants in female rats

Two groups of female rats had crystalline estradiol benzoate, progesterone and cholesterol implanted in the medial hypothalamus. One group was ovariectomized (OVX) and weighed approximately 300 g. The second group was adrenalectomized and ovariectomized (ADX-OVX) and weighed approximately 250 g. EB placed in the ventromedial hypothalamus significantly reduced feeding in the OVX animals; progesterone and cholesterol had no effect. In contrast, progesterone increased feeding in the lean ADX-OVX animals; EB and cholesterol were without effect. The most effective progesterone placements were in the dorsal medial hypothalamic nuclei. The data are discussed in terms of EB and progesterone influencing a hypothalamic set point for body weight.     

Role of the stria terminalis in food intake and body weight in rats

Previous studies have shown that lesions of the posterodorsal amygdala result in hyperphagia and obesity in female rats. In the present study, lesions of the stria terminalis at its most dorsal point (before it separates into dorsal and ventral components) also resulted in hyperphagia and excessive weight gains in female rats compared to female rats with sham lesions, as did coronal knife cuts anterior to the ventromedial hypothalamus. Identical lesions and knife cuts did not elevate food intake or weight gains in male rats compared to male control animals. Examination of the anterograde degeneration with the amino-cupric-silver method in the brains of two female rats with hypothalamic knife cuts revealed degenerating terminals in the capsule of the ventromedial hypothalamus and in the premammillary nuclei, two classic indicators of damage to the dorsal component of the stria terminalis. No degenerating axon terminals were observed in the paraventricular nucleus. Differences from previous studies that used male rats were attributed to a sex difference for the effects of amygdaloid and ventromedial hypothalamic lesions. It is proposed that the posterodorsal amygdala, dorsal component of the stria terminalis, and ventromedial hypothalamus are part of an inhibitory pathway in the regulation of feeding behavior.     

Sexual dimorphism in the regulation of caloric intake and body weight of rats fed different diets

Female, androgenized female (AF), and male rats were given access to 1 of 3 diets—chow (C), high-dextrose (D-chow:dextrose, 2:1), and high-fat (F-chow:Crisco, 2:1) for 2 months. Caloric intake (CI), water intake, and body weights were monitored daily. Responses to gonadectomy and a single injection of estradiol benzoate (EB) were also studied. For females, F- and C-fed rats had comparable CI's, whereas D-fed rats chronically ate much less. For males, F-fed rats overate, whereas C- and D-fed rats had comparable CI's. The pattern of CI of AF rats fed the 3 diets was intermediate between that of males and females. Male rats were less responsive to the anorexic effects of EB than were the other two groups, and the F-diet potentiated the anorexic effects of EB in all three groups. Results are discussed in terms of a sex difference in the hypothalamic regulation of feeding behavior which is modulated by gonadal hormones.