Huddling,locomotor, and nest-building behaviors of furred and furless Siberian hamsters

Rodents living in the cold employ both behavioral and physiological mechanisms to achieve thermoregulation. We examined the impact of fur loss on behavioral thermoregulation in cold-challenged Siberian hamsters (Phodopus sungorus). Intact female hamsters exposed to an ambient temperature (T(a)) of 5 degrees C increased their general locomotor activity by 50% relative to animals maintained at 23 degrees C. At both T(a)'s, fur removal resulted in substantial increases in daily food intake (37% and 22% at 5 and 23 degrees C, respectively) but did not affect the amount of locomotor activity; increased food intake after fur loss evidently is not caused by increases in locomotor activity. Furred hamsters housed in groups of three at 5 degrees C consumed 16% less food per day than did singly housed individuals. Fur removal resulted in identical 39% increases in food intake in group- or singly housed animals. Energy savings that accrued from huddling were identical in furred and furless animals; this behavior conserves energy even in the absence of an insulative pelage. The availability of nesting material resulted in an 18% reduction in food consumption in intact animals kept at 5 degrees C. The increase in food intake produced by fur removal was attenuated by approximately 80% when furless animals had access to nesting material. Huddling and nest-building behaviors each ameliorate energetic challenges posed by absence of fur; animals that concurrently employ several modes of thermoregulation realize substantial energy savings in the cold.     

Spontaneous meal patterns in female rats with and without access to running wheels

Rats display strong behavioral rhythms during the ovarian cycle. During estrus, food intake is minimal due to a decrease in meal size, and locomotor activity is maximal. To investigate how activity influences feeding patterns across the ovarian cycle, we used a computerized system to monitor spontaneous meal patterns in intact, cycling female rats with and without access to running wheels. We found that running wheel access decreased dark meal frequency, increased dark meal size, and increased 24-h water intake during each phase of the ovarian cycle. In contrast, body weight, 24-h food intake, and the ovarian rhythms of reduced food intake, meal size, and body weight during estrus were not affected by running wheel access. In particular, the reduction in food intake during estrus was due to a selective reduction in dark meal size, not dark meal frequency, and this occurred independent of wheel access. These data indicate that estrus-related changes in spontaneous meal patterns and locomotor activity are independently controlled and that the reduction in food intake during estrus involves a selective change in the neurobiological controls of meal size.     

Behavior and body weight changes under intermittent exposure to cold in C57BL/6J mice

This experiment examined effects of the intermittent exposure to cold. C57BL/6J mice were exposed to cold (4-5 degrees C) for six hours in light (L-cold group) or dark (D-cold group) period and their wheel-running and drinking activities, daily amounts of food and water intake, and body weight were analyzed. Wheel running and drinking decreased during cold exposure, while they increased in postcold period. These behavioral changes were more clearly found in the D-cold group. Body weight of the D-cold group was kept constant for all days of cold exposure, while that of the L-cold group tended to increase. These results are discussed from the view points of adaptive significance of postcold behaviors and the relationship between behavioral and physiological adaptations.     

Behavioral and cardiovascular changes in the chronic mild stress model of depression

Depression is a multifaceted psychological disorder that involves changes in behavior, neuroendocrine function, and physiological responses. The present study investigated multiple behavioral and cardiovascular consequences in the chronic mild stress (CMS) rodent model of depression. Rats were exposed to 4 weeks of CMS followed by 4 weeks of a stress-free recovery period. Sucrose intake, a measure of anhedonia, and spontaneous locomotor activity were measured weekly throughout the study, and cardiovascular function tests were conducted at the completion of the protocol. The results indicate that CMS results in anhedonia and reduced locomotor activity, as well as elevated heart rate (HR), reduced HR variability, and elevated sympathetic cardiac tone. The behavioral effects of CMS recovered to baseline (prestress) levels during the recovery period; however, cardiovascular changes were observed following the recovery of sucrose intake and activity levels. The present findings suggest that behavioral changes that are indicative of anhedonia and locomotor alterations associated with depression are dissociable from long-term cardiovascular changes induced by CMS.     

The physiological and behavioral effects of subchronic intracisternal administration of TGF-beta in rats: comparison with the effects of CRF

We studied the physiological and behavioral effects of subchronic intracisternal administration of transforming growth factor-beta (TGF-beta) for 7 days. Subchronic intracisternal administration of TGF-beta significantly inhibited the increase in body weight of rats but did not affect food intake. In the measurement of locomotor activity after the final intracisternal administration on day 7, the total count for 1.5 h increased significantly in the TGF-beta group compared with the vehicle group. However, that for 10 h was not different between both groups. Furthermore, significant elevations in oxygen consumption were observed in the TGF-beta group during both light and dark phase. Subchronic TGF-beta treatment induced a significant decrease in the number of total leukocytes and lymphocytes and the relative weight of the thymus, and a significant increase in brown adipose tissue weight. Corticotropin-releasing factor (CRF) is the primary neuroendocrine factor released in response to stress. Subchronic treatment with CRF, as a positive control, significantly affected body weight, food intake, oxygen consumption, total leukocyte and lymphocyte counts, and thymus and adrenal weight. Subchronic TGF-beta administration partially mimicked the stress responses, implicating a role for TGF-beta in the brain in stress.     

Behavioral and electrophysiological changes following microinjections of colchicine into the substantia nigra.

Male Sprague-Dawley rats received bilateral microinjections of colchicine (2 or 4 μg in 1 μl) into the substantia nigra. During the first 2 days the animals were hyperactive, intense gnawing and chewing were observed, and food intake was significantly increased. During the next 3 or 4 days, activity, food and water intakes and body weight gain were markedly reduced; the behavior was similar to that previously observed following damage to the substantia nigra and nigrostriatal pathway from 6-hydroxydopamine or electrolytic lesions. This period of hypophagia and hypodipsia was followed by a rebound increase in food and water intake for several days until body weight returned to normal levels. Field potentials recorded from the caudate nucleus in response to electrical stimulation of the substantia nigra were reduced in amplitude during the first 4 days following microinjections of colchicine into the substantia nigra and recovered by Day 7.These reversible behavioral effects of microinjections of colchicine into the substantia nigra confirm the importance of the nigrostriatal pathway in motor and ingestive behaviors.     

Sex-specific modulation of anxiety and locomotion after neonatal exposure to pregnenolone sulfate

Neurosteroids may influence adult behavior and endocrine function since early in development. To test this hypothesis, Sprague-Dawley pups from both sexes were injected with pregnenolone sulfate (PREG-S) from postnatal (PN) day 1 to 14. Pubertal onset in females was determined by monitoring the day of vaginal opening. After vaginal opening, the pattern of estrous cycle was monitored for three consecutive cycles. During adulthood, anxiety and locomotor activity were assessed with an automated elevated plus maze (EPM) and automated activity monitors, respectively. After behavioral assessment, body weight, gonadal weight, and plasma levels of sex hormones were measured. Neonatal exposure to PREG-S produced anxiolytic effects in females but not males. The opposite effect was seen in males, suppression of locomotor behaviors without changes in anxiety. The day of vaginal opening, gonadal weight, and plasma levels of hormones in adult animals were not altered by neonatal treatment. We suggest that PREG-S exposure during neonatal development can have an impact in anxiety and locomotor behaviors during adulthood in a sex-specific manner.     

Chronic food restriction: enhancing effects on drug reward and striatal cell signaling

Chronic food restriction (FR) increases behavioral sensitivity to drugs of abuse in animal models and is associated with binge eating, which shares comorbidity with drug abuse, in clinical populations. Behavioral, biochemical and molecular studies conducted in this laboratory to elucidate the functional and mechanistic bases of these phenomena are briefly reviewed. Results obtained to date indicate that FR increases the reward magnitude and locomotor-activating effects of abused drugs, and direct dopamine (DA) receptor agonists, as a result of neuroadaptations rather than changes in drug disposition. Changes in striatal DA dynamics, and postsynaptic cell signaling and gene expression in response to D-1 DA receptor stimulation have been observed. Of particular interest is an upregulation of NMDA receptor-dependent MAP kinase and CaM Kinase II signaling, CREB phosphorylation, and immediate-early and neuropeptide gene expression in nucleus accumbens (NAc) which may facilitate reward-related learning, but also play a role in the genesis of maladaptive goal-directed behaviors. Covariation of altered drug reward sensitivity with body weight loss and recovery suggests a triggering role for one of the endocrine adiposity hormones. However, neither acute nor chronic central infusions of leptin or the melanocortin 3/4 receptor agonist, MTII, have attenuated d-amphetamine reward or locomotor activation in FR rats. Interestingly, chronic intracerebroventricular leptin infusion in ad libitum fed (AL) rats produced a sustained decrease in food intake and body weight that was accompanied by a reversible potentiation of rewarding and locomotor-activating effects of d-amphetamine. This raises the interesting possibility that rapid progressive weight loss is sufficient to increase behavioral sensitivity to drugs of abuse. Whether weight loss produced by leptin infusion produces the same neuroadaptations as experimenter-imposed FR, and whether any of the observed neuroadaptations are necessary for expression of increased behavioral responsiveness to acute drug challenge remain to be investigated.     

General activity in intact and hypophysectomized rats after administration of melanocyte-stimulating hormone (MSH), melatonin, and PRO-LEU-GLY-NH 2

The effects of melanocyte-stimulating hormone (MSH), melatonin, and Pro-Leu-Gly-NH₂ on levels of general locomotor activity were investigated in hypophysectomised and intact rats. General activity was not altered by the hormones studied. Body weight, food ingestion, and water intake were also measured and found to be unchanged. The findings reduce the possibility that alterations in activity account for the behavioral changes previously observed after administration of MSH, melatonin, or Pro-Leu-Gly-NH₂.     

Fluoxetine-maintained obese humans: effect on food intake and body weight

The effects of fluoxetine on food intake, body weight, and mood of obese individuals was examined in a 16-week inpatient/outpatient study. Six male and eight female obese volunteers began the study (four male and five females completed all phases of the study). They lived in a residential laboratory during three one-week inpatient periods separated by a 5-week and an 8-week outpatient period. Following an initial 4-day placebo baseline, participants were maintained on fluoxetine (60 mg/day) for the remainder of the study. Food intake parameters (total daily energy intake, macronutrient intake, mean number of eating bouts, interbout interval), body weight, subjective effects, and task performance were measured several times during the day during inpatient periods; food intake questionnaires were completed daily during the outpatient periods. Fluoxetine significantly reduced daily energy intake derived from fat, carbohydrate, and protein by decreasing the mean number of eating bouts per day throughout the study. No other food intake parameter was affected. Body weight was significantly reduced after 7 weeks, but not after 16 weeks of daily fluoxetine administration. These results indicate that fluoxetine reduced food intake for at least 16 weeks in nondepressed obese individuals without specifically affecting carbohydrate intake. Weight that was lost during the first few weeks of daily fluoxetine administration was subsequently regained even though food intake remained reduced. Therefore, fluoxetine maintenance does not appear promising as a sole long-term therapy for obesity.     

Locomotor activity and ingestive behavior after damage to ascending serotonergic systems

The effects of electrolytic midbrain raphe lesions on ingestive behavior and locomotor activity of rats were compared to those produced by intracerebral injections of 5,7 dihydroxytryptamine (5,7 DHT) at various points along the ascending serotonergic pathways. Only electrolytic lesions of the median and/or dorsal raphe nuclei produced significant changes in food intake, water intake, body weight gain, and wheel running activity. Intracerebral injections of 5,7 DHT, a selective serotonergic neurotoxin, had no effect on any of these variables. However, 5,7 DHT induced lesions produced decreases in forebrain synaptosomal uptake of serotonin which were equivalent to, or greater than, those resulting from electrolytic lesions of the midbrain raphe nuclei. Failure of 5,7 DHT injections to replicate the behavioral changes resulting from electrolytic lesions of the midbrain raphe nuclei suggests that loss of ascending serotonergic projections was not responsible for the behavioral effects that followed the electrolytic lesions.     

The effects of exercise on the neuronal response to food cues

Increased physical activity is associated with successful long-term weight loss maintenance due to mechanisms likely more complex than simply increased energy expenditure. The impact of physical activity on the central regulation of food intake may be an important mechanism of this effect. The objective of this study was to examine the effects of exercise training and acute exercise on the neuronal response to food cues as well as eating behaviors. fMRI was performed in the fasted state at baseline and again after a 6 month progressive exercise intervention (supervised, 5 days/wk) both with and without an acute exercise bout in 12 overweight/obese (5 women, 7 men; BMI 33 ± 4 kg/m(2)) healthy adults. fMRI data were acquired while subjects were presented with visual stimuli of foods of high hedonic value as compared to neutral control objects. Questionnaires on eating behaviors, ratings of appeal and desire for foods, and ratings of appetite (hunger, satiety, prospective intake) using visual analog scales were also performed at baseline and again after the 6-month exercise intervention. While only a trend was observed for a reduction in body weight (102 ± 5 to 99 ± 6 kg, p=0.09), a significant reduction in fat mass was observed (36.4 ± 2.8 to 33.7 ± 3.2 kg, p=0.04), although as expected changes in fat mass were variable (-10.0 to +3.7 kg). Chronic exercise was associated with a reduction in the neuronal response to food, primarily in the posterior attention network and insula. A significant positive correlation between the change in fat/body mass and the change in insula response to food cues with chronic exercise was observed. An acute exercise bout attenuated the effects of chronic exercise. The exercise intervention, however, did not impact any of the measures of appetitive behavior. In summary, despite no effects on behavioral measures of appetite, chronic exercise training was associated with attenuation in the response to visual food cues in brain regions known to be important in food intake regulation. The insula, in particular, appears to play an important role in the potential exercise-induced weight loss and weight loss maintenance.     

Physiological and behavioral responses to intermittent starvation in C57BL/6J mice

The dual intervention point model states that body mass is controlled by upper and lower intervention points, above and below which animals (and humans) intervene physiologically to bring their body mass back into the acceptable range. It has been further suggested that the lower intervention point may be defined by the risk of starvation, while the upper intervention point may be defined by the risk of predation. The objective of the present study was to test whether the risk of starvation determines the lower intervention point and to examine the physiological and behavioral mechanisms that underpin the regulation of body mass, when the risk of starvation is increased. Sixty-four mice were exposed to random days of complete fasting or 50% food restriction and their body mass and fat mass responses were measured. Food intake, physical activity and body temperature were measured throughout the experiment. In addition, plasma leptin and insulin, triglyceride and non-esterified fatty acids, along with hypothalamic neuropeptides gene expression in the arcuate nucleus were assessed after 13 and 42 days of treatment. We found that C57BL/6J mice increased body mass and fatness in response to a short-term (13 days) intermittent fasting, which was restored to baseline as the treatment was prolonged. In contrast, intermittently 50% food restricted mice showed no significant changes in body mass or fatness. Over the first 13 days of treatment the data were consistent with the dual intervention point model as the mice showed both increased body mass and adiposity over this period. Over the more protracted period of 42 days the effect waned and was therefore inconsistent with the model. The body mass and fat mass gains in intermittently fasted mice were mainly accounted for by increased food intake. Elevated NPY gene expression after 13 days (three 24 h fasting events) may have driven the increase in food intake. However, no changes were observed in such neuropeptides as POMC, CART, AgRP, Ob-Rb and SOCS 3 or circulating levels of leptin, insulin, NEFA and TG. Hypothermia during fasting days may have also contributed to the increase in body mass. Over 42 days of treatment (nine 24 h fasting events) cumulative food intake was not affected by intermittent starvation. However physical activity, mainly activity during the light phase was lowered suggesting an adaptation to unpredictable starvation. Overall, mice exhibited different behavioral and physiological responses to intermittent starvation depending on the duration of treatment.     

Behavioral and physiological responses to stress are affected by high-fat feeding in male rats.

Interactions between monoaminergic neurochemistry and macronutrient intake have been frequently shown. Because monoaminergic systems in the brain are also closely involved in behavioral and physiological stress responses it can be hypothesized that differences in the macronutrient composition of diets are reflected in these responses. The present studies, therefore, were designed to assess the consequences of a change in dietary macronutrient composition on a variety of physiological and behavioral responses (both acute and long-term) to a number of stressors. The effect of chronic high-fat (HF; 61% kcal from fat) feeding on the stress responses was compared with controls receiving regular high-carbohydrate (HC; 63% kcal from carbohydrates) laboratory chow. Rats were kept on this diet for at least 2 months before they were exposed to either psychological (social defeat) or physiological (lipopolysaccharide, LPS, administration) stress. At baseline, chronic HF feeding caused a slight, but significantly reduction in body temperature relative to that observed in HC-fed rats. Following social defeat or LPS injection, HF feeding caused a faster recovery of the body temperature increase relative to animals on the HC diet. Stress-induced suppression of home cage locomotor activity and body weight gain were also reduced by HF feeding. The serotonergic 5-HT(1a) receptor hyposensitivity that was observed in HC-fed rats 2 weeks after stress was absent in the HF regimen. Although the present results cannot be readily interpreted as showing purely beneficial effects of high-fat diets on stress responsivity, the findings in the present study do encourage further investigation of possible ameliorating effects of high-fat diets on aspects of the behavioral and physiological response stress.     

Gonadal hormones and behavioral regulation of body weight

Gonadal hormones have important effects on the behaviors that determine body weight in laboratory rats (i.e., eating, locomotor activity, and thermoregulatory behavior). These effects are most evident in the female where there are consistent, predictable changes in these behaviors which are correlated with fluctuations in plasma hormone levels during estrous cycles, puberty, pregnancy, or after gonadectomy and replacement therapy. Estradiol, which seems to be the principal ovarian steroid affecting body weight, may act directly on separate neural loci to: (a) inhibit food intake and (b) stimulate locomotor activity, possibly by lowering the set-point of a hypothalamic lipostat. Estradiol does not affect eating and running in prepubertal female rats, perhaps because of influences of pituitary hormone(s) at this age. Ovarian hormones also alter the taste preferences of rats and may be responsible for the changes in self-selection of dietary components during different reproductive states. Some implications of this research are discussed and possible directions for future research suggested.     

Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice

Smoking appears to increase overall levels of stress, despite self-reports that men and women smoke to control symptoms of anxiety. The overall incidence of anxiety disorders is also significantly higher in women. This study examined whether behavioral sensitivity to chronic nicotine varies across sexes in mice. Male and female C57BL/6J mice were exposed chronically to nicotine in the drinking water (50, 100, or 200 microg/ml) and tested for locomotor activation and anxiety-like behavior in the elevated plus maze (EPM). Female mice were less sensitive to the locomotor activating effects of chronic nicotine. Whereas both males and females showed increases in locomotor activity at the highest (200 microg/ml) concentration of nicotine, only males showed locomotor activation at the middle (100 microg/ml) concentration. The decreased sensitivity in females could not be explained by reduced nicotine intake compared to males. In the EPM, nicotine produced an anxiogenic-like response in females, but had no effect in males. Treatment with the high (200 microg/ml) dose of nicotine reduced the amount of time spent in the open arms of the EPM in female, but not male mice. No differences in the anxiogenic-like response to chronic nicotine was observed between beta2-subunit knockout and wildtype mice, suggesting that beta2-subunit containing nicotinic receptors do not mediate the anxiogenic-like response to chronic nicotine in females. This shows that female mice have an anxiogenic-like response to chronic nicotine, but are less sensitive to nicotine's psychostimulant properties, which may be related to the increased relapse to smoking following abstinence in women.     

Previous chronic ACTH administration does not protect against the effects of acute or chronic stress in male rats

The effect of previous chronic ACTH administration on the physiological response to acute and chronic immobilization stress was studied in adult male rats. Chronic ACTH administration slightly reduced food intake and drastically inhibited body weight gain. Serum corticosterone levels were similar in saline- and ACTH-treated rats twenty hours after the last administration. However, the corticosterone response to 1 hr immobilization was greatly reduced by previous ACTH administration. When the exposure to the stressor was prolonged up to 18 hours, the corticosterone response was similar in saline, and ACTH-treated rats. While body weight loss caused by starvation and acute stress was lower in ACTH-treated rats, stomach ulceration was greater in the latter animals. Although ACTH-treated rats showed higher body weight gain than saline-treated animals during chronic immobilization, this was probably due to catch-up growth as food intake inhibition caused by the stressor was similar in the two groups. Pituitary-adrenal adaptation to the repeated stressor was the same in saline- and ACTH-treated rats. Therefore, the effects of previous ACTH treated on the physiological response to either acute or chronic stress appear to be mixed, depending on the variable studied.     

Effect of glucagon-like peptide-1 and -2 on regulation of food intake, body temperature and locomotor activity in the Japanese quail

To investigate the physiological roles of glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) in avian species, we elucidated the effect of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of GLP-1 and GLP-2 on food intake, body temperature and gross locomotor activity in adult Japanese quail. Both i.p. and i.c.v. administration of GLP-1 suppressed food intake at 2, 4 and 12h after administration. Moreover, both i.p. and i.c.v. administration of GLP-1 significantly decreased both body temperature and gross locomotor activity 2h after administration. On the other hand, both i.p. and i.c.v. administration of GLP-2 had no effect on food intake, body temperature or gross locomotor activity. These results suggest that GLP-1 may have an important role in the regulation of food intake, body temperature and locomotor activity while GLP-2 may have no apparent effect on feeding regulation in adult Japanese quail.     

Dietary Self-monitoring in Patients with Obstructive Sleep Apnea

Self-monitoring of food intake is a cornerstone of behavioral weight loss interventions, but its use has not been evaluated in the treatment of obese patients with obstructive sleep apnea (OSA). This pilot study described patterns of adherence to dietary self-monitoring in obese patients with OSA and determined associations between self-monitoring and weight loss, psychosocial functioning, and adherence to continuous positive airway pressure treatment. Participants completed a 6-week behavioral weight loss intervention focused on dietary self-monitoring. Approximately one-third of participants were adherent to self-monitoring throughout the course of the intervention and experienced more weight loss than those who did not self-monitor regularly. More frequent dietary self-monitoring also appeared to be associated with adherence to other health behaviors. These preliminary data suggest that use of dietary self-monitoring may be beneficial for promoting weight loss and adherence to other important health behaviors in OSA patients.     

Effects of food deprivation on water intake induced by intermittent delivery of salted liquid food

The water intake of rats maintained through food deprivation at 70, 80, 90, and 100% of free-feeding body weights was examined under conditions where a small amount of sweetened condensed milk containing 8% sodium chloride was presented at one-minute intervals. For each of two subjects, number of licks and milliliters of water consumed varied inversely with body weight. This finding agrees with earlier reports concerning the effects of food deprivation on adjunctive behaviors induced by intermittent delivery of dry food.