Cocaine and serotonin: a role for the 5-HT1A receptor site in the mediation of cocaine stimulant effects

Cocaine induced locomotor stimulant effects are generally attributed to coc aine effects on brain dopamine. In this report, we present evidence that th e 5-hydroxytryptamine(1A) (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)t etralin (8-OHDPAT) and the 5-HT1A antagonist, N-[2-[4-(2-methoxyphenyl)-1-" piperazinyl]ethyl]-N-2-pyridinyl-cycylhexanecarboxaminde maleate (WAY 10063 5) can enhance or block, respectively, the locomotor stimulant effects indu ced by cocaine. In two separate experiments, rats administered cocaine (10 mg/kg) exhibited a locomotor stimulant effect and decreased grooming behavi or compared to saline treated rats. Pretreatment with the 5-HT1A agonist, 8 -OHDPAT (0.2 mg/kg) enhanced and pretreatment with the 5-HT1A antagonist, W AY 100635 (0.4 mg/kg) eliminated the locomotor stimulant effect of cocaine. Neither the 8-OHDPAT nor WAY 100635 effects were attributable to effects o n the behavioral baseline. The 8-OHDPAT and WAY 100635 had opposite effects on Grooming behavior. 8-OHDPAT decreased and WAY 100635 increased grooming . Neither treatment, however, affected the grooming suppression induced by cocaine. Ex vivo biochemical measurements indicated that neither 8-OHDPAT o r WAY 100635 affected brain dopamine metabolism or cocaine availability in brain. Both treatments affected 5-HT metabolism and altered the effect of c ocaine on 5-HT metabolism. 8-OHDPAT increased and WAY 100635 decreased coca ine effects on 5-HT metabolism. Cocaine and 8-OHDPAT but not WAY 100635 inc reased corticosterone. Altogether, these findings indicate that the 5-HT1A receptor site may be an important target for the development of pharmaco th erapies for the treatment of cocaine abuse. (C) 2001 Elsevier Science B.V. All rights reserved.