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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