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Journal of Neuroscience, Vol 15, 7181-7188, Copyright © 1995 by Society for Neuroscience
Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion
V Deroche, M Marinelli, S Maccari, M Le Moal, H Simon and PV Piazza
INSERM U259, Universite de Bordeaux II, France.
Repeated exposures to stress sensitize motor and addictive effects of drugs
of abuse. Recently, it has been shown that stress-induced behavioral
sensitization depends on the secretion of glucocorticoids. We investigated
if sensitization of dopamine-dependent effects of psychostimulants and
opioids was influenced by glucocorticoid. Sensitization of the dopaminergic
response to drugs is considered the neural substrate of behavioral
sensitization and has been implicated in vulnerability to drug abuse.
Dopamine-dependent effects of psychostimulants and opioids were evaluated
by injecting either amphetamine into the nucleus accumbens (10
micrograms/side) or morphine into the ventral tegmental area (VTA) (1
microgram/side). The locomotor response to psychostimulants and opioids
injected in these brain areas depends on the mesencephalic dopaminergic
transmission. Drug-induced locomotion was compared in male rats in which
corticosterone secretion was either in +tct or experimentally suppressed by
an adrenalectomy associated with a substitutive treatment reproducing basal
levels of the hormone. Eight days of food restriction (80% of the initial
body weight) were used as a stressor. Suppression of stress-induced
corticosterone secretion abolished food restriction-induced sensitization
of the locomotor effects of intra-accumbens amphetamine and intra-VTA
morphine. This effect was corticosterone dependent since the restoration of
corticosterone levels in the range of those induced by stress totally
reinstates sensitization. Our results suggest that glucocorticoids control
stress-induced sensitization by changing the sensitivity of the
mesencephalic dopaminergic transmission to drugs of abuse. Since
dopaminergic effects of drugs are related to their addictive properties,
secretion of glucocorticoids may be one of the factors determining the
enhanced vulnerability to drugs observed in stressed subjects.
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