mise à jour du
16 février 2007
Am J Physiol
1988;255(6 Pt 2):R914-22.
Effects of alpha-MSH on sleep, behavior, and
brain temperature: interactions with IL 1
Opp MR, Obal F Jr, Krueger JM.
Department of Physiology and Biophysics, University of Tennessee, Memphis


Changes in rabbit sleep-wake activity, brain temperature (Tbr), and behavior were studied after intracerebroventricular injections of a putative endogenous antipyretic, alpha-melanocyte-stimulating hormone (alpha-MSH), and of an endogenous pyrogen, interleukin 1 (IL 1-beta). alpha-MSH (0.1-50.0 micrograms) dose dependently increased wakefulness (W) and decreased Tbr, non-rapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). NREMS was more sensitive than REMS to the suppressive effects of low alpha-MSH doses. EEG slow-wave activity in NREMS decreased after alpha-MSH treatment. alpha-MSH elicited stretching, yawning, and signs of sexual excitation. IL 1 (20 and 40 ng) induced fever and excess NREMS. alpha-MSH administered 30 min after IL 1 (40 or 20 ng IL 1 + 0.1, 0.5, or 5.0 micrograms alpha-MSH) significantly attenuated IL 1-induced fever and excess NREMS. IL 1 failed to alter the behavioral effects of alpha-MSH. Despite alpha-MSHs effect on rabbit behavior, total motor activity time did not increase, indicating that increased W after alpha-MSH cannot be attributed to behavioral activation. These results suggest that, besides acting as an endogenous antipyretic, alpha-MSH might be involved in regulation of IL 1-induced sleep.
Interleukin 1 (IL 1) is a cytokine that plays a key role in a variety of host defense responses, including induction of fever and acute phase responses. IL 1 is produced by a number of cell types, such as monocytes, keratinocytees, endothelia, and glia, and IL1-mRNA is constituently expressed in the central vous system. IL 1 also has the capacity to enhance non-rapid-eye-movement sleep (NREMS), and this IL 1 activity may result from IL 1 of glial origin. Thus IL 1-like activity varying with the sleep-wake cycle has been reported in cerebrospinal fluid (CSF). It has been proposed that endogenous IL 1 might be involved in physiological sleep regulation.
Recent observations suggest that a-melanocyte-stimulating hormone a-MSH, i.e., adrenocorticotropic hortie (ACTH)-(1-13), a proopiomelanocortin-derived peptide, acts as a physiological inhibitor for at least some IL1 actions. This notion stems mainly from the finding that administration of a-MSH attenuates fever elicited IL 1 in rabbits and guinea pigs, whereas immunoneutralization of endogenous a-MSH by intra-cerebroventricular injection of anti-a-MSH antibodies prolongs IL 1-induced fever. In addition, release a-MSH from the septal region of rabbit brain has been demonstrated in response to IL 1-induced fever. aMSH also interferes with other IL 1 actions; it inhibits the capacity of IL 1 to stimulate hepatic synthesis acute phase proteins, induce neutrophilia, and enhance plasma levels of corticosterone in vivo. Furthermore, IL 1 stimulation of proliferation of murine thymocytes in vitro may also be inhibited by a-MSH, though the latter finding is controversial.
The aim of these experiments was to determine the effects of intracerebroventricular injections of a-MSH on sleep-wake activity and brain temperature (Tbr) and to ascertain whether a-MSH attenuates the IL 1 enhanced NREMS and Tbr. Because possible a-MSH-stimulated behavioral actions, e.g., stretching and yawing, sexual excitation, and grooming, might interfere sleep, the behavioral effects of the peptide were also sturdied.
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