The effects of blocking brainstem CRF receptors on stress responsiveness in rats
Miragaya, Joanna Rodrigues
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Stress is a reaction of the body to a critical situation and it produces many different responses, including endocrine, autonomic, metabolic, immune, and behavioral, which vary according to the type and period of exposure to a stressor. Centrally released corticotrophin-releasing factor (CRF) and its homologues Urocortin (Ucn), Ucn II, and Ucn III, appear to be the initiators of responses to stress. There are two receptor subtypes for these neuropeptides, CRFR1 and CRFR2, and each receptor plays a different role in stress-induced responses. It is well established that acute stress can decrease body weight and inhibit food intake of rats. Several brain nuclei known to control energy balance respond to stress, however, the major initiator and/or regulator of stress-induced changes in energy balance has not been identified. Therefore, we investigated whether areas adjacent to the fourth ventricle were involved in regulating body weight and food intake during acute stress. Experiments described here used two types of acute stress to produce weight loss and inhibit food intake; repeated restraint and mild stress. The first set of Experiments tested whether CRF infusions into the fourth ventricle would inhibit food intake in overnight food-deprived rats, and whether CRFRs antagonists would prevent this decrease in food intake. The second set of Experiments tested whether antagonism of CRFRs in brain nuclei adjacent to the fourth ventricle would prevent stress-induced changes in body weight and food intake. In the third set of Experiments, we tested whether antagonism of CRFRs in areas adjacent to the fourth ventricle before stress would prevent activation of the hypothalamus and/or brain nuclei known to respond to stress. The outcome of these Experiments lead us to conclude that: (1) CRF in areas adjacent to the fourth ventricle plays a role in regulating feeding behavior in unstressed animals, (2) stress-induced decrease in body weight and inhibition of food intake are mediated by different pathways, depending upon the type of stress, (3) the brainstem may play an important role in regulating energetic responses to mild stress, (4) and that nuclei in the brainstem may be responsible for some of these stress-induced responses.