The selective serotonin(1A)-receptor antagonist WAY 100635 blocks behavioral stimulating effects of cocaine but not ventral striatal dopamine increase.

An increase in the extracellular dopamine (DA) concentration is generally accepted as an important neurochemical mediator of the behavioral effects of cocaine. Cocaine induced increases in serotonergic (5-HT) activity also appears to be involved in these effects. Here we describe the effects of the 5-HT(1A)-receptor antagonist WAY 100635 on the behavioral and neurochemical effects of cocaine. In-vivo microdialysis was used in behaving rats to measure extracellular concentration of DA in the nucleus accumbens (Nac). Four groups of animals received one of the following drug combinations: WAY 100635 (0.4 mg/kg) and cocaine (10 mg/kg), saline and cocaine (10 mg/kg), WAY 100635 (0.4 mg/kg) and saline, or saline and saline. The injections were administered i.p. and spaced 20 min apart. The pretreatment with WAY 100635 significantly attenuated the locomotor stimulant effects of cocaine without altering the DA overflow in the Nac. WAY 100635 itself did not modify locomotion or the extracellular DA concentration in the Nac. These results indicate that (1) the 5-HT(1A)-receptor is an important component in the mediation of cocaine locomotor stimulant effects, and (2) an increase in the extracellular DA concentration in the Nac might be a necessary but is not a sufficient condition for the locomotor stimulant effects of cocaine. Copyright 2002 Elsevier Science B.V.