The 5-HT_1A receptor modulates the effects of cocaine on extracellular serotonin and dopamine levels in the nucleus accumbens

The regulation of extracellular levels of serotonin (5-HT) and dopamine in response to cocaine by 5-HT_1A receptors was examined using in vivo microdialysis and the 5-HT_1A receptor antagonist 4-(2′-methoxy- )-phenyl-1-[2′-(N-2″-pyridinyl)-p-fluorobenzamido-]ethyl-piperazine (p-MPPF). Pretreatment with p-MPPF significantly augmented the increase in extracellular levels of both 5-HT and dopamine in the nucleus accumbens produced by systemic administration of cocaine. Levels of 5-HT or dopamine were unaffected by p-MPPF given alone. Extracellular levels of 5-HT and dopamine were increased dramatically by cocaine infused locally into the nucleus accumbens. Systemic injection of cocaine given during the cocaine infusion reduced 5-HT and dopamine levels, presumably by activating inhibitory 5-HT and dopamine autoreceptors outside of the locus of infusion. The reduction of 5-HT and dopamine levels by systemic cocaine during accumbal infusion was blocked by pretreatment with the 5-HT_1A receptor antagonist p-MPPF. Taken together, these findings suggest that the 5-HT_1A autoreceptor acts to modulate the effects of cocaine on both 5-HT and dopamine levels in the nucleus accumbens.