THE LONG-TERM ACUTE PHASE-LIKE RESPONSES THAT FOLLOW ACUTE STRESSOR EXPOSURE ARE BLOCKED BY ALPHA-MELANOCYTE-STIMULATING HORMONE

Both intracerebroventricular (i.c.v.) IL-1 beta and exposure to inesca pable tail shock (IS) activate acute phase responses (APRs) that inclu de increases in core body temperature (CBT), increases in hypothalamic -pituitary-adrenal activity, decreases in carrier proteins such as cor ticosterone binding globulin (CBG), aphagia and adipsia. A variety of data suggested that stressors produce APRs by inducing brain IL-1 beta . The current series of studies further explored this possibility by d etermining whether the functional IL-1 beta antagonist, alpha-melanocy te-stimulating hormone (alpha-MSH(1-13)), would block IS-induced APRs. Immediately following i.c.v. alpha-MSH(1-13) administration, rats wer e exposed to a single session of 100, 5 s, 1.6 mA ISs, or control trea tment (home cage control). alpha-MSH(1-13) blocked IS-induced increase d CBT, increased plasma corticosterone (CORT), decreased CBG, aphagia and adipsia 24 h after IS. The inhibitory effects of alpha-MSH(1-13) w ere shown not to be a consequence of alpha-MSH(1-13) producing its act ions 24 h after its administration because alpha-MSH(1-13) given 24 h before IS did not block IS-induced increased CBT and CORT during IS. A dditionally, alpha-MSH(1-13), given 24 h before IS, had no effect on i ncreased CBT, increased CORT, decreased CBG, adipsia, or aphagia 24 h after IS. These data provide support for a specific mode of action for i.c.v. alpha-MSH(1-13), namely blockade of APRs with no impact on acu te hyperthermia or increased levels of CORT produced during IS. (C) 19 98 Elsevier Science B.V. All rights reserved.