Chronic effects of acute stress in rats

Project: Research project

Description

DESCRIPTION (provided by applicant): Studies in this proposal investigate the chronic effects of acute stress on long-term regulation of body weight. Rats exposed to 3 hours of restraint on each of 3 consecutive days lose weight on the days of stress and gain weight when stress ends, but do not return to the weight of their non-stressed controls. Thus, repeated restraint provides a unique model in which acute stress results in a chronic reduction in body weight. Identification of mechanisms responsible for this sustained reduction in body weight will provide new information on the normal regulation of body weight and may lead to novel strategies for successful maintenance of weight loss in overweight individuals. Although we have determined that initiation of weight loss is dependent upon activation of central corticotropin releasing factor Type 2 (CRF2) receptors adjacent to the 3rd and/or 4th ventricle, we have not identified sustained changes in the basal neurochemical or endocrine status of the animals during the post-stress period. We have, however, shown that feeding rats a high-fat (40 percent kcal fat) diet exaggerates the response to stress by inducing a greater weight loss and have observed that rats that have been exposed to repeated restraint stress show an exaggerated endocrine and hypophagic response to a subsequent mild stress. We hypothesize that acute stress causes a chronic hyper-reactivity of aspects of the CRF system that are both stress-responsive and are involved in the regulation of energy homeostasis. Hyper-reactivity of the CRF system may prevent recovery of body weight in stressed rats. The sensitivity of these same systems also is influenced by diet composition to increase stress responsiveness in rats fed a high-fat diet. Specific Aim 1 will test whether rats that have been exposed to repeated restraint stress exhibit an exaggerated neurochemical, energetic and behavioral response to a subsequent mild stress, which would be indicative of an increased reactivity of the CRF system. Specific Aim 2 will test whether feeding a high-fat diet results in a hyper-responsiveness of the CRF system or a suppression of the post-stress down-regulation of CRF activity, to clarify whether increased stress responsiveness is caused by the same mechanisms in high-fat fed rats as in rats that have been exposed to repeated restraint. Specific Aim 3 will identify nuclei in the hypothalamus and brainstem that are critical for stress-induced weight loss.
StatusFinished
Effective start/end date3/1/042/28/10

Funding

  • National Institutes of Health: $251,231.00
  • National Institutes of Health: $286,610.00
  • National Institutes of Health: $258,733.00
  • National Institutes of Health: $264,960.00
  • National Institutes of Health: $251,231.00

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Weight Loss
Body Weight
Fats
High Fat Diet
Diet
Fourth Ventricle
Weights and Measures
Ideal Body Weight
Third Ventricle
Hypothalamus
Brain Stem
Weight Gain
Homeostasis
Down-Regulation
Maintenance

ASJC

  • Medicine(all)