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Journal of Neuroscience, Vol 15, 7189-7195, Copyright © 1995 by Society for Neuroscience
Stress-induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion
F Rouge-Pont, M Marinelli, M Le Moal, H Simon and PV Piazza
INSERM U259, Universite de Bordeaux II, France.
Secretion of glucocorticoids seems to control stress-induced sensitization
of the behavioral effects of drugs of abuse by acting on the mesencephalic
dopaminergic transmission, the principal neural substrate of sensitization.
In order to investigate the mechanisms of this interaction between
glucocorticoids and dopamine, we studied the sensitization of the increase
in extracellular concentration of dopamine induced by cocaine in male rats
in which corticosterone secretion was either intact or blocked.
Extracellular concentrations of dopamine were evaluated in the nucleus
accumbens of freely moving animals by means of microdialysis. Metyrapone,
an inhibitor of corticosterone synthesis, was used to block stress-induced
corticosterone secretion. Food-restriction (90% of the initial body weight)
was the stressor used to induce sensitization. It was found that metyrapone
(100 mg/kg s.c. twice a day for 8 d) suppressed stress- induced
sensitization of the increase in accumbens dopamine induced by cocaine (10
mg/kg, i.p.) and sensitization of cocaine-induced locomotion Metyrapone
suppressed both the development and the expression of sensitization. Thus,
sensitization was equally blocked when the metyrapone treatment started
either 1 d before the start of food-restriction or 8 d later, that is, when
food-restriction-induced sensitization to cocaine was already established.
In conclusion, our results suggest that glucocorticoids modify
sensitization of the behavioral effects of cocaine by acting on
extracellular concentrations of dopamine. Since addictive properties of
psychostimulants seem mediated by the increase in extracellular
concentrations of dopamine they induce, these findings may have
implications for the development of new therapeutic strategies of
addiction.
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