Involvement of 5-HT 1B receptors within the ventral tegmental area in regulation of mesolimbic dopaminergic neuronal activity via GABA mechanisms: a study with dual-probe microdialysis

Abstract

This study was designed to assess the involvement of 5-HT 1B receptors within the ventral tegmental area (VTA) in the regulation of mesolimbic dopaminergic transmission. Dual-probe microdialysis was performed in freely moving adult Sprague–Dawley rats with one probe within the VTA and the other within the ipsilateral nucleus accumbens (NACC). Drugs were administered into the VTA via retrograde dialysis. Dialysates from both the VTA and the NAC were collected for determination of dopamine (DA) and gamma-aminobutyric acid (GABA) by high-performance liquid chromatography with electrochemical detection. Intra-tegmental infusion of CP 93129 (20, 40, and 80 μM), a 5-HT 1B receptor agonist, increased extracellular DA concentrations in a concentration-dependent manner not only in the NACC but also in the VTA, indicating increased mesolimbic DA neuron activity. Administration of CP 93129 at 80 μM into the VTA also significantly decreased extracellular GABA concentrations in this region. Co-infusion of the 5-HT 1B receptor antagonist SB 216641 (10 μM), but not the 5-HT 1A receptor antagonist WAY 100635 (10 μM) or the 5-HT 1D/1A receptor antagonist BRL 15572 (10 μM), antagonized not only the effects of intra-tegmental CP 93129 (80 μM) on VTA DA and NAC DA but also on VTA GABA. The results suggest that activation of VTA 5-HT 1B receptors increases mesolimbic DA neuron activities. The increased DA neuron activity may be associated, at least in part, with the 5-HT 1B receptor-mediated inhibition of VTA GABA release.