Adult vs. adolescent rats differ in biobehavioral responses to chronic nicotine administration

More than 90% of smokers begin smoking during adolescence, suggesting that nicotine's actions may differ in adults vs. adolescents in ways that render adolescents vulnerable to smoking initiation. This experiment tested the hypothesis that nicotine's biobehavioral actions differ in adult and adolescent rats. Forty-two male (21 adolescents, 21 adults) and 41 female (21 adolescents, 20 adults) Sprague–Dawley rats were administered saline or 12 mg/kg/day nicotine via osmotic minipump for 21 days. Body weight, feeding, and locomotion (horizontal activity, vertical activity, center time) were measured before, during, and after saline or nicotine administration. Nicotine's effects depended on age and sex. Nicotine reduced body weight and feeding of adult males and females, and of adolescent males, but not of adolescent females. In addition, adolescent males were more sensitive than adults or adolescent females to nicotine's activity-enhancing effects. In cessation, nicotine-exposed adolescent males continued to exhibit greater activity than saline-exposed animals. Results indicate that nicotine's biobehavioral actions differ depending on age and sex.     

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     

Different effects of chronic nicotine treatment regimens on body weight and tolerance in the rat

The effect of different chronic nicotine administration regimens on body weight and the development of tolerance was examined in female rats. Groups of animals were either treated with nicotine via a subcutaneous continuous release pellet or via two injections each day of either a high (5.6 mg/kg) or low (0.8 mg/kg) dose. Both the Pellet and Low injection groups showed a progressive weight loss during nicotine treatment followed by a weight gain upon cessation of treatment, but the time course and size of these weight changes were quite distinct. In contrast, the High injection group gained weight during the 17 days of nicotine treatment. Tolerance, as measured by locomotor activity following an acute injection of nicotine 1 week after cessation of chronic nicotine treatment, was evident only in the Low injection group. This study demonstrates that the regimen in which nicotine is administered is an important factor in determining the behavioral effects produced by chronic nicotine treatment.     

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.     

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.     

Noise stress does not modulate effects of smoking/nicotine on β-endorphin, cortisol, ACTH, glucose, and mood

Noise-dependent effects of smoking multiple cigarettes on subjective state and blood concentrations of ACTH, β-endorphin, cortisol, and glucose were assessed in a repeated measures design where noise level (high versus minimal) was crossed with nicotine dose (quasi-ad lib own brand versus 1.0 mg FTC nicotine machine-delivered dose versus 0.05 mg FTC nicotine machine-delivered dose). Cortisol and ACTH were increased by nicotine, but not by noise and there was no noise by dose interaction. In contrast, nicotine did not increase β-endorphin in either noise condition and there was no dose by noise interaction for β-endorphin. However, noise was associated with a modest increase in β-endorphin. The effects of nicotine on blood glucose varied as a function of the number of cigarettes smoked. However, the effects of nicotine on glucose, hormones, and subjective state did not vary as a function of noise stress. Received: 9 October 1995 / Final version: 28 October 1996     

The acute and subchronic effects of a brain-penetrating, neurotensin-1 receptor agonist on feeding, body weight and temperature

The neurotensin-1 (NT1) receptor has been implicated in mediating a number of important neurotensin effects. We have found that PD149163, a selective, brain-penetrating, NT1 receptor agonist, produces a number of therapeutic-like preclinical effects after peripheral administration including pro-cognitive, antipsychotic and anxiolytic effects. In this study, we investigated PD149163's effect on food intake and thermal regulation, two physiological processes thought to be mediated by NT1 receptors.Brown Norway rats and leptin-deficient mice (ob/ob) mice were administered subcutaneous PD149163 (0, 0.1, 0.25, or 1 mg/kg) for ten consecutive days. Weight and 24-h food intake were measured in mice and rats and core body temperature was also measured in rats.PD149163 significantly decreased food intake in rats and ob/ob mice and no tolerance was demonstrated to this effect over the course of the study. PD149163-treated animals exhibited weight loss compared to saline-treated animals. PD149163 produced hypothermia as expected but this effect did show tolerance over the course of the study, unlike feeding. The results suggest that NT1 receptor agonists are candidates for treatment of obesity and that somewhat different mechanisms are involved in NT1-induced feeding regulation and temperature regulation.     

The effects of long-term nicotine treatment on locomotion,exploration and memory in young and old rats

To assess the effects of long-term treatment with nicotine on several behavioral measures (locomotor activity, exploratory efficiency, habituation, short-term and long-term memory) of young (5 months) and old (22 months) rats in a hexagonal tunnel maze, nicotine was added to the drinking water (0, 20 or 50 mg/l) for up to 131 experimental days. With the exception of effects on exploratory efficiency, young and old rats did not differ in their response to the drug. Nicotine decreased body weight throughout the experiment. Nicotine treatment reduced water intake during the first 30 min of the daily 4.5 h access to drinking water. Nicotine increased locomotor activity throughout the experiment. When nicotine treatment was discontinued during a 7-day withdrawal period, locomotor activity immediately dropped to control values. Intertrial habituation was not affected by nicotine. Long-term nicotine treatment had an attenuating effect on exploratory efficiency in young rats; however, the drug did not influence performance in tasks measuring spatial memory. Finally, age increased weight, decreased locomotor activity and impaired exploratory efficiency and short-term memory. Age, however, did not affect the performance of the long-term memory task.     

Tripelennamine effects on body and organ weights, water intake, and several behaviors of rats

The effects of 14 daily injections of tripelennamine on several dependent measures were determined in groups of rats that received 0.0 (vehicle only), 2.0, 4.0, 8,0, or 16.0 mg/kg of the drug.l Tripelennamine did not affect body weights, organ weights (heart, liver, adrenals, kidneys), or blood glucose levels. Daily water intake was, however, directly and significantly related to tripelennamine dose. The drug failed to influence performance in a grasping response assay, or locomotion as measured in running wheels when rats received footshocks immediately before assessment of locomotion. Tripelennamine did significantly reduce locomotion when rats were not shocked before testing. Nociception, as measured via a hot-plate assay, also was altered by the drug. Here, rats exposed to 16 mg/kg evinced paw-lick latencies far greater than those that received lower doses. These results indicate that tripelennamine produced observable behavioral effects at doses which are not obviously toxic.     

氯氮平、利培酮与齐拉西酮对精神分裂症患者体重及血糖的影响研究

目的探讨氯氮平、利培酮、齐拉西酮三种抗精神病药物对精神分裂症患者体重及血糖的影响。方法将190例精神分裂症患者随机分成氯氮平、利培酮、齐拉西酮三组,分别给予单药治疗6个月。于治疗前、及治疗第1、2、3、6个月末监测患者体重及空腹血糖。结果治疗2个月后,氯氮平组、利培酮组体重较治疗前增加,差异具有统计学意义(P<0.05),治疗3个月后,氯氮平组、利培酮组血糖较治疗前增加,差异具有统计学意义(P<0.05),齐拉西酮组治疗前后体重和血糖差异无显著性(P>0.05)。结论氯氮平、利培酮对患者的体重及血糖均有影响,而齐拉西酮的影响不显著。     

Effects of chronically administered fluoxetine and fenfluramine on food intake,body weight and the behavioural satiety sequence

Rats were administered fenfluramine (FF: 3 mg/kg) or fluoxetine (FX: 6 mg/kg) daily for 3 weeks. On acute administration, FF suppressed consumption of 35% sucrose (in a 40 min test) and overnight chow intake. Repeated administration saw the rapid development of extensive tolerance to these effects. FF had no effects on body weight, and no withdrawal effects were apparent. FX reduced chow intake and body weight throughout the treatment period, but there was evidence of some tolerance to the suppression of chow intake and sucrose drinking. Following FX withdrawal, normal body weight was restored in 4 days; food intake was normal during this period. A delayed rebound hyperphagia commenced on day 5 of withdrawal, and persisted for at least 6 days. The behavioural satiety sequence (drinking -activity - grooming - resting) was disrupted by acute FF; on chronic treatment, FF advanced the onset of postprandial resting, but also increased drinking time. FX advanced the behavioural satiety sequence on acute administration, but not after chronic treatment. We consider the implications of these results for the use of resting behaviour as an indicator of postprandial satiety.     

Nicotine modulates effects of stress on acoustic startle reflexes in rats: dependence on dose,stressor and initial reactivity

Cigarette smokers report that one reason for smoking is that smoking helps them cope with stress, but there is conflicting evidence as to whether nicotine reduces physiological and behavioral responses to stress. The acoustic startle reflex amplitude, pre-pulse inhibition, and habituation of the reflex provide quantifiable measures of behavioral reactivity that may be sensitive to stress-induced changes that are altered by nicotine. In the present experiment, rats classified as high and low reactors according to baseline startle amplitudes were administered nicotine (6 or 12 mg/kg/day) or saline by osmotic minipump for 11 days. On day 11, animals were acutely stressed by restraint or observation of restraint of conspecifics prior to startle measurement. Nicotine and stress each independently increased acoustic startle amplitude and amount of pre-pulse inhibition, but in combination, the effect of restraint stress and 12 mg/kg nicotine were indistinguishable from saline-treated, non-stressed controls. In contrast, the 6 mg/kg nicotine dose enhanced effects of both restraint and observation stressors on startle amplitude and pre-pulse inhibition. Animals classified as highly reactive prior to treatment were more responsive to nicotine, stress, and the combination, suggesting that initial reactivity is an important determinant of drug and stress effects. Results indicate that nicotine can both reduce and enhance stress effects on reflex amplitude and pre-pulse inhibition depending upon nicotine dose, stressor, and individual differences in reactivity.This research was supported by USUHS protocol RO72AR. The views contained herein are the private ones of the author and do not necessarily reflect those of the Uniformed Services University of the Health Sciences or the Department of Defense.     

Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake, body weight change, and pruritus in rats

Rationale  The cannabinoid CB1 selective antagonist SR141716A (Rimonabant) has been shown to decrease body weight in laboratory animals and humans. Furthermore, SR141716A can elicit scratching behavior in rodents, a behavior that has been hypothesized to contribute to SR141716A-induced decrease in food intake. Although childhood obesity is a rising health issue, it is unknown whether SR141716A is equipotent at modulating food intake and other CB1-mediated behaviors in younger subjects. Objective  To determine whether CB1 receptor blockade is equipotent at modulating food and water intake, body weight, and scratching behavior, the effect of a range of SR141716A doses on these behaviors in food-restricted postnatal day (P) 18, 28, and 60 male rats was investigated. Brain concentrations of SR141716A were determined in each age group. Results  SR141716A dose- and age-dependently suppressed food and water intake and body weight gain and elicited head scratching, with the most potent effects observed in P18 and P28 rats. Brain concentrations of SR141716A were significantly elevated in P18 rats relative to P28 and P60 rats. SR141716A-elicited head scratching was attenuated by the 5-HT_2A/2C antagonist ketanserin. Conclusions  SR141716A is more potent at modulating food intake and head scratching in very young animals; these differences can be attributed to an increase in brain penetration of SR141716A for P18 but not for P28 and P60 rats. In addition, SR141716-elicited head scratching is modulated by 5HT receptor antagonism and is not a contributing factor to SR141716A's anorectic effects.     

The effects of diet, ad Libitum feeding, and moderate and severe dietary restriction on body weight, survival, clinical pathology parameters, and cause of death in control Sprague-Dawley rats.

A 2-year study was conducted in Sprague-Dawley rats to compare the effects of ad libitum (AL) feeding and dietary restriction (DR) on body weight, survival, cause of death, and clinical pathology parameters. Three groups of 120 rats/sex each received the following daily rations of a maintenance rodent diet: ad libitum (AL group); 75% of adult AL food consumption (25% DR group); and 45% of adult AL food consumption (55% DR group). Among the 3 groups, there were generally no differences in relative (food intake per gram of body weight) food consumption. Compared to the AL group, decreased body weight gain occurred in DR groups and was associated with an increase in survival proportional to the DR rate. The main cause of death was pituitary adenomas in all groups. Decreases in total leukocyte, segmented neutrophil, lymphocyte, and platelet counts occurred in the 55% DR group. In serum biochemistry, there were decreases in total protein, albumin, total and HDL cholesterol, and total calcium, and increases in alkaline phosphatase activities and chloride in 55% DR females, as well as decreases in triglycerides in the 55% DR group and in 25% DR females. Results of urinalyses showed decreases in urine volume and protein, and increases in urinary pH in both DR groups. In conclusion, a DR rate of approximately 25% appears to be appropriate for Sprague-Dawley rats in toxicity and carcinogenicity assays to improve survival without impairing growth and routine clinical pathology parameters.