Nucleus accumbens serotonin1A receptors control cocaine-induced hyperactivity but not local serotonin increase: an in vivo microdialysis study.

The nucleus accumbens (Nac) is an important structure for cocaine-induced hyperactivity and receives a dense serotonergic (5-HT) innervation. Previous studies showed that a systemic activation of 5-HT(1A) receptors potentiates cocaine-induced hyperlocomotion, but attenuates the cocaine-induced 5-HT increase in the Nac. In order to address the role of Nac 5-HT(1A) receptors in the control of cocaine-induced and spontaneous behavioural activity and local 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT(1A)-receptor agonist, 8-OH-DPAT (0, 1 and 10 microM), was applied locally into the Nac by reverse dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The Nac 5-HT(1A)-receptor activation potentiated cocaine-induced hyperlocomotion, but attenuated rearing behaviour dose-dependently. Parallel to that, the cocaine-induced increase in Nac 5-HT dialysate level was unaffected, as were the decreases in 5-HIAA and DOPAC dialysate levels after cocaine. In saline treated rats, the local application of 8-OH-DPAT into the Nac affected neither spontaneous behavioural activity nor 5-HT, 5-HIAA or DOPAC dialysate levels in the Nac. These data suggest that Nac 5-HT(1A) receptors exert a bi-directional control of cocaine-induced hyperactivity, while not affecting spontaneous behaviour. Furthermore, accumbal 5-HT(1A) receptors do not appear to be directly involved in the acute effects of cocaine on 5-HT, 5-HIAA or DOPAC levels in the Nac.