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

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Annual rept. 11 Feb 2003-10 Feb 2004

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The experiments under Specific Aim 1 were continued and the work related to Hypothesis 1 under this aim was completed. In these experiments dual-probe microdialysis was performed with one probe in the ventral tegmental area VTA and the other in the ipsilateral nucleus accumbens NACC. CP 93129 20, 40, and 80 muM, a 5-HT1B receptor agonist, was infused into the VTA of separate groups of rats, Dialysates from the VTA and NACC were collected for assay of dopamine DA and GABA. In another experiment, SB-216641 10 muM, a 5-HTlB receptor antagonist, BRL-15572 10 muM, a 5-HTlBlA receptor antagonist, or WAY-100635 10 muM, a 5-HTlA receptor antagonist was inflised into the VTA for 40 min, and then co-infused with CP 93129 80 muM for another 60 min. The results showed that intra tegmental CP 93129 increased DA concentrations in the VTA in a concentration-dependent manner. Administration of CP 93129 at 80 muM, but not 20 or 40 muM, into the VTA also significantly decreased GABA in this region. Co-infusion of SB-216641, but not BRL-15572 or WAY-100635, antagonized not only the effects of intra-tegmental CP 93129 80 muM on VTA DA and NACC DA but also on VTA GABA. The results suggest that activation of VTA 5-HTlB receptors increases mesolimbic DA neuron activities. The increased DA neuronal activity may be associated, at least in part, with the 5-HTlB receptor-mediated inhibition of VTA GABA release. The work related to Specific Aim 2 was also started in Year 2. After several months of efforts, the method of genotyping 5-HTlB receptor knockout KO and their counterparts wild-type WT mice has been developed and a number of KO and WT mice were generated at the Pis lab. Microdialysis experiments have already been started in these mice.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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