INTERMITTENT MORPHINE ADMINISTRATION INDUCES A LONG-LASTING SYNERGISTIC EFFECT OF CORTICOSTERONE ON DOPAMINE D1 RECEPTOR FUNCTIONING IN RATSTRIATAL GABA NEURONS

Glucocorticoid receptor (GR)-mediated facilitation of striatal dopamin ergic (DA) neurotransmission has been proposed to play a role in behav ioral sensitization induced by intermittent exposure to drugs of abuse or stressors. Searching for possible common neuronal substrates acted upon by drugs of abuse and corticosterone, we addressed the question as to whether such a facilitatory effect is apparent (i.e., persists) in primary cultures of rat striatum subsequent to intermittent (prenat al) morphine administration. As previously observed in striatal slices of morphine-treated rats, intermittent morphine exposure in vivo caus ed a long-lasting increase in DA D1 receptor-stimulated adenylyl cycla se activity, that appeared to persist in primary cultures of rat stria tal gamma-aminobutyric acid (GABA) neurons. Subsequent in vitro exposu re of these striatal neurons to corticosterone or dexamethasone, simul tanously activating GR and mineralocorticoid receptors (MR), about dou bled this adaptive effect of previous in vivo morphine administration. The selective MR agonist aldosterone was ineffective in this respect. Prior in vivo morphine treatment also enhanced the stimulatory in vit ro effect of corticotropin releasing hormone (CRH) on adenylyl cyclase in cultured GABA neurons. However, the enhanced CRH receptor function ing was not potentiated by in vitro corticosterone exposure. Activatio n of GR by corticosterone did not facilitate the increase in D1 recept or efficacy induced by sustained activation of muscarinic receptors in cultured striatal neurons. These data indicate that previous intermit tent morphine administration induces a long-lasting synergistic effect of corticosterone on enhanced striatal DA neurotransmission at the le vel of postsynaptic D1 receptors. Moreover, the induction of this neur oadaptation seems to display opioid receptor selectivity and its long- term expression may be confined to D1 receptors. Since exposure to dru gs of abuse or stressors not only increase striatal DA release but als o plasma corticosterone levels, we hypothesize that this adaptive phen omenon in DA-sensitive GABA neurons is involved in the expression of m orphine-induced long-term behavioral sensitization to drugs of abuse a nd stressors. (C) 1997 Wiley-Liss, Inc.