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Journal of Neuroscience, Vol 14, 2724-2731, Copyright © 1994 by Society for Neuroscience
Corticosterone circadian secretion differentially facilitates dopamine- mediated psychomotor effect of cocaine and morphine
M Marinelli, PV Piazza, V Deroche, S Maccari, M Le Moal and H Simon
INSERM U259, Universite de Bordeaux II, France.
Studies of intravenous self-administration and psychomotor effects of drugs
have recently suggested that stress-induced corticosterone secretion may be
an important factor determining vulnerability to drugs of abuse. In this
report, we studied if basal physiological corticosterone secretion
modulates sensitivity to cocaine and morphine, and if changes in the
reactivity of mesolimbic dopaminergic (DA) neurons, one of the principal
substrates of drug-reinforcing effects, are involved. For this purpose we
determined the psychomotor effects of these drugs in animals in which
corticosterone secretion was suppressed by adrenalectomy and in
adrenalectomized animals submitted to different corticosterone replacement
therapies designed to mimic (1) only the diurnal levels of the hormone,
obtained by the subcutaneous implantation of 50 mg corticosterone pellets;
(2) only the nocturnal levels, obtained by adding corticosterone (50
micrograms/ml) to the drinking solution during the dark period; and (3) the
entire circadian fluctuation, obtained by combining the two previous
treatments. Locomotor response to cocaine and morphine was studied after
both systemic and central injections, into the nucleus accumbens for
cocaine and into the ventral tegmental area for morphine. These sites were
chosen because stimulant effects of cocaine and morphine injected in these
structures are dopamine dependent. Our results show that suppression of
corticosterone by adrenalectomy reduced the locomotor response to cocaine
and morphine, injected both systemically and centrally. The reinstatement
of diurnal levels of corticosterone totally reversed adrenalectomy's
effects on the behavioral response to cocaine, whereas the reestablishment
of the entire corticosterone circadian fluctuation (diurnal plus nocturnal
levels) was necessary to reverse the response to morphine.(ABSTRACT
TRUNCATED AT 250 WORDS)
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