The effects of repeated restraint stress on energy balance and behavior of mice with selective deletion of CRF receptors.

Mice subjected to restraint stress (RRS) daily for 3 days lose weight. Once stress ends they are slow to recover the weight loss and exhibit increased anxiety and hypothalamus-pituitary-adrenal (HPA) activity in response to novel stressors. We tested the effect of RRS in mice deficient in corticotropin releasing factor receptor one (CRFR1-KO) or two (CRFR2-KO). Wild type (WT) and CRFR2-KO, but not CRFR1-KO, mice lost weight during RRS. All adrenalectomised mice lost weight and CRFR2-KO controls stopped gaining weight on the days of RRS. WT RRS mice returned to the weight of their controls 8 days after restraint. CRFR2-KO mice showed high levels of anxiety in an elevated plus maze (EPM) 11 days after RRS and in a light/dark choice test 14 days after RRS. CRFR1-KO mice displayed low anxiety in both tests, but RRS decreased EPM exploration. By contrast, exploration increased in RRS ADX mice. Testing in the EPM increased serum corticosterone level in all WT and CRFR2-KO mice. Corticosterone increased in RRS CRFR1-KO mice compared with their controls. These results suggest that CRFR1 are required for stress-induced weight loss, but that hyper-reactivity of the HPA axis in RRS mice exposed to a subsequent novel stress is independent of CRFR1.

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.

Water maze performance and changes in serum corticosterone levels in zinc-deprived and pair-fed rats.

The aims of the present study were (1) to evaluate the learning and short- and long-term memory of zinc-deprived (ZD) and pair-fed (PF) rats in a Morris water maze (MWM) and (2) to monitor the serum corticosterone levels of these rats before and after swimming. Young Sprague-Dawley rats (aged 27-31 days) consumed AIN-93G diet for 10 days, and then were separated into ad libitum control (CT), PF and ZD groups. The zinc content of the diet was 25-30 ppm (CT and PF) or <1 ppm (ZD). After 17 days on experimental diets, a MWM was used to test spatial cognition. Delayed-matching-to-place (DMP) test results indicate that both zinc deprivation and food restriction had no effect on short-term memory. The PF rats exhibited significantly impaired learning and thigmotaxia (i.e., wall hugging) in the learning test. The PF group also demonstrated less preference for the target zone in the first 15 s of the probing test. When the total 120 s of the probing test was considered, there were no differences in preference for the target zone, but thigmotaxia was greater in the PF than the CT group. The only behavioral change of the ZD group was thigmotaxia observed during the 120-s probing test following training, indicating the increment of anxiety. Morning basal corticosterone levels before swim training were significantly elevated in the PF group on Day 15 of dietary treatment, whereas a significant elevation of the basal corticosterone level in the ZD group was not statistically significant until Day 22. The data indicate an association between impaired learning, poor searching strategy and elevated corticosterone in the PF group. In contrast, the ZD rats showed normal cognitive performance but had elevated corticosterone and increased anxiety-like behavior (thigmotaxia).