Activation of 5-HT2A/2C receptors within the nucleus accumbens increases local dopaminergic transmission

This study was designed to assess the involvement of the 5-hydroxytryptamine (5-HT)2A/2C receptor subtypes in the regulation of in vivo dopamine release in the rat nucleus accumbens (NAC). Extracellular dopamine (DA) in the NAC was measured using intracerebral microdialysis coupled with an HPLC-EC system. 5-HT2A/2C receptor agonist, (+/-)-1-(4-lodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) and antagonists, LY-53,857 and ketanserin, were all administered via a dialysis probe into the NAC. The results showed that perfusion with DOI at concentrations of 10, 50, 100, and 300 microM elicited a significant and concentration-dependent increase in extracellular DA. DA levels returned to control values within 40-60 min after terminating DOI perfusion. The increased DA induced by perfusion with 100 microM DOI was sensitive to sodium channel blockade with tetrodotoxin, and antagonized by co-perfusion with either LY-53,857 (25 and 50 microM) or ketanserin (50 microM). Perfusion with 50 microM LY-53,857 alone failed to alter basal levels of DA. The results suggest that local application of DOI increases DA release via a receptor-mediated process, and are consistent with the concept that activation of 5-HT2A/2C receptors within the NAC can augment dopaminergic transmission in this region although these receptors are not involved in the regulation of basal accumbal DA release.