Ethanol and Mesolimbic Serotonin/Dopamine Interactions via 5HT-1B Receptors

According to Statement of Work, Hypothesis 1 under Specific Aim 1 was tested during Year 1 .To this end, dual-probe microdialysis was employed and the 5-HT1B receptor agonist CP 93129 used. The experiments were performed in freely-moving rats. One probe was in the ventral tegmental area (VTA) and the other in the ipsilateral nucleus accumbens (NACC). Artificial cerebrospinal fluid (AC SF) alone and ACSF with three concentrations of CP 93129 (20, 40, and 80 micronM) were infused respectively into the VTA of separate groups of rats for 60 min. Dialysates from the VTA and NACC were collected at 20-min intervals for determination of NACC DA and VTA GABA via HPLC systems. The results showed that administration of CP 93129 caused significant increases of extracellular DA concentrations in the NACC in a concentration-related manner. The maximum increases of NACC DA produced by 20, 40 and 80 micronM of CP 93129 were 163%, 181%, and 214% of baseline, respectively. The determination of GABA levels in the VTA is presently under way and has not been completed yet. The results suggest that activation of VTA 5-HTlB receptors by focally applied CP 93129 increases DA transmission in the ipsilateral NACC.