PERFUSATE SEROTONIN INCREASES EXTRACELLULAR DOPAMINE IN THE NUCLEUS-ACCUMBENS AS MEASURED BY INVIVO MICRODIALYSIS

The effects of local application of serotonin (5-HT) on extracellular levels of dopamine (DA) in the nucleus accumbens (N. ACC) were assessed using in vivo microdialysis. At a perfusate flow rate of 0.3 mul/min the baseline dialysate concentration of DA was 2.1 +/- 0.7 nM (mean +/- S.E.M.; n = 5) and significantly increased to 142 +/- 18%, 220 +/- 47% and 332 +/- 35% of baseline when 0.1 muM, 0.2 muM and 0.4 muM concentrations of 5-HT were included in the perfusate. Perfusate 5-HT concentrations below 0.1 muM had no effect on dialysate DA. The in vivo dialysis efficiency for 5-HT was found to be 39 +/- 12%, and thus the concentrations of 5-HT reaching the extracellular space at the surface of the dialysis membrane were estimated to be 40,80 and 160 nM for the 0.1, 0.2 and 0.4 muM 5-HT perfusates, respectively. The serotonin-induced increase in dialysate DA was attenuated by co-perfusion of 0.4 muM 5-HT with 4 muM concentrations of pindolol (a relatively non-specific 5-HT1 antagonist; 151 +/- 7% vs. 332 +/- 35% baseline dialysate DA for 5-HT/antagonist and 5-HT-only perfusates, respectively), LY 53,857 (a specific 5-HT2 antagonist; 130 +/- 17% vs. 332 +/- 35%) and MDL 7222 (a specific 5-HT3 antagonist; 143 +/- 19% vs. 332 +/- 35%). While the contributions of the 5-HT, receptor subtype are unclear, the inhibitory efficacy of a highly specific 5-HT2 antagonist and-an antagonist specific to 5-HT2 and 5-HT3 receptors suggest that both of these receptor subtypes are involved in the serotonin-induced DA increase in the N. ACC.