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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH068281-04
Application #
7183484
Study Section
Special Emphasis Panel (ZRG1-NMB (03))
Program Officer
Vicentic, Aleksandra
Project Start
2004-03-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
4
Fiscal Year
2007
Total Cost
$251,231
Indirect Cost
Name
University of Georgia
Department
Nutrition
Type
Other Domestic Higher Education
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Harris, Ruth B S (2017) Repeated restraint stress lowers the threshold for response to third ventricle CRF administration. Horm Behav 89:64-68
Scherer, Isabell J; Holmes, Philip V; Harris, Ruth B S (2011) The importance of corticosterone in mediating restraint-induced weight loss in rats. Physiol Behav 102:225-33
Chotiwat, C; Kelso, E W; Harris, R B S (2010) The effects of repeated restraint stress on energy balance and behavior of mice with selective deletion of CRF receptors. Stress 13:203-13
Legendre, Ariadne; Papakonstantinou, Emilia; Roy, Marie-Claude et al. (2007) Differences in response to corticotropin-releasing factor after short- and long-term consumption of a high-fat diet. Am J Physiol Regul Integr Comp Physiol 293:R1076-85
Harris, Ruth B S; Palmondon, Julie; Leshin, Stephen et al. (2006) Chronic disruption of body weight but not of stress peptides or receptors in rats exposed to repeated restraint stress. Horm Behav 49:615-25
Legendre, Ariadne; Harris, Ruth B S (2006) Exaggerated response to mild stress in rats fed high-fat diet. Am J Physiol Regul Integr Comp Physiol 291:R1288-1294