Serotonergic properties of cocaine: Effects on a 5-HT₂ receptor-mediated behavior and on extracellular concentrations of serotonin and dopamine

The present study examined the ability of cocaine to produce behavioral and neuropharmacological effects through serotonin (5-HT) systems. Pretreatment with fluoxetine or cocaine potentiated the head-shake response to the 5-HT precursor, 5-hydroxytryptophan (5-HTP; 75 mg/kg), a behavior mediated by the activation of 5-HT₂ receptors. This effect was antagonized by the selective 5-HT₂ receptor antagonist ketanserin (1 mg/kg). In contrast, pretreatment with the selective norepinephrine uptake inhibitor desipramine (10 mg/kg) or the selective dopamine (DA) uptake inhibitor GBR 12909 (32 mg/ kg) failed to potentiate the head-shake response. The effects of cocaine on extracellular concentrations of DA and 5-HT in the nucleus accumbens were examined using in vivo microdialysis in a separate group of anesthetized rats. Cocaine (10 mg/ kg) increased the extracellular concentrations of DA and 5-HT by 300-350% over baseline levels. Cocaine's ability to increase the head-shake response and to increase extracellular concentrations of 5-HT may be due to its ability to block 5-HT uptake.