Modification of cocaine-induced behavioral and neurochemical effects by serotonin1A receptor agonist/antagonist in mice

Administration of cocaine causes a locomotor stimulant effect and increases extracellular levels of serotonin (5‐HT) and dopamine (DA) in the brains of rodents. Previous studies show that 5‐HT1A receptor agonist and antagonist modify the cocaine‐induced behavioral and neurochemical effects in the rats. However, the role of the 5‐HT system on the effects of cocaine has not been studied in the prefrontal cortex. The present study examined in ddY‐strain male mice the effects of the 5‐HT1A receptor agonist osemozotan and the receptor antagonist WAY100635 on cocaine‐induced locomotor stimulant effect and increases in extracellular levels of 5‐HT and DA in the prefrontal cortex. The cocaine‐induced locomotor stimulant effect was attenuated by osemozotan and enhanced by WAY100635. The cocaine‐induced increase in extracellular levels of 5‐HT was attenuated by osemozotan, and enhanced by WAY100635. The cocaine‐induced increase in extracellular levels of DA was enhanced by osemozotan, but not affected by WAY100635. These results suggest that the prefrontal 5‐HT system plays a pivotal role in the locomotor stimulant effect of cocaine in mice. Synapse 60:479–484, 2006. © 2006 Wiley‐Liss, Inc.