Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum

Glucocorticoid hormones exert strong influences on central neurotransmitter systems. In the present work, we examined the functional consequences of c orticosterone suppression on the dopaminergic transmission in the dorsolate ral striatum by studying the expression of Fos-like proteins and extracellu lar dopamine levels. Glucocorticoid hormones were suppressed by adrenalecto my, and the specificity of the effects assessed by restoring physiological plasmatic corticosterone concentrations. We show that, in the dorsolateral striatum, glucocorticoids modify postsynaptic dopaminergic transmission. Su ppression of glucocorticoids decreased the induction of Fos proteins in res ponse to a direct agonist of dopamine D-1 receptors (SKF 82958, 1.5 mg/kg, i.p.), but not the release of dopamine induced by morphine (2 mg/kg, s.c.) or the density of the limiting enzyme of dopamine synthesis, tyrosine hydro xylase. In contrast to the dopaminergic response to morphine, the response to cocaine (15 mg/kg, i.p.) was modified by the suppression of corticostero ne. In this case, adrenalectomy increased cocaine-induced changes in extrac ellular dopamine but did not modify the expression of Fos-like proteins. Th is absence of changes in cocaine-induced Fos-like proteins might result fro m a compensatory mechanism between the increase in the dopaminergic respons e and the decrease in the functional activity of dopamine D-1 receptors. Th e increased dopaminergic response to cocaine also contrasts with the decrea sed response previously observed in the shell of the nucleus accumbens [Bar rot et al. (2000) Eur. J. Neurosci., 12, 973-979]. The present data highlig ht the profound heterogeneous influence of glucocorticoids within dopaminer gic projections.