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Vol. 281, Issue 3, 1401-1407, 1997
Psychobiologie des Comportements adaptatifs, INSERM U259
Université de Bordeaux II, Domaine de Carreire, Rue Camille
Saint-Saëns, 33077 Bordeaux Cedex, France
Observations suggest that corticosterone, the principal glucocorticoid
hormone in the rat, can modulate the behavioral effects of drugs of
abuse. In this report, the influence of corticosterone on intravenous
self-administration of cocaine was studied. In the first experiment,
cocaine intravenous self-administration in adrenalectomized rats and in
adrenalectomized rats receiving corticosterone replacement treatments
was studied as a function of corticosterone concentrations and as a
function of cocaine doses (0.025, 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg/infusion). In a second experiment, we tested, in intact rats, the
effect of different doses of corticosterone (0.09, 0.18, 0.37, 0.58, 0.75 mg/kg) on the reinstatement of an extinguished cocaine
self-administration behavior. It is reported that adrenalectomy
markedly shifts the cocaine self-administration dose-effect curve
downward. This effect was dose-dependently reversed by corticosterone;
a complete restoration being obtained for corticosterone levels in the
range of those induced by stress. Corticosterone administration also
precipitated dose-dependently the reinstatement of cocaine
self-administration. The maximal effect was obtained for a dose of
corticosterone producing an increase in plasma levels similar to the
increase produced by an intense stress. In conclusion, our results show
that glucocorticoids facilitate the reinforcing effects of cocaine and
support the hypothesis that glucocorticoids are one of the biological
factors determining vulnerability to substance abuse.
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