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PO2-1-78

Analysis of activated cells in the dopaminergic neuron by ethanol

[Speaker] Masahiro Shibasaki:1
[Co-author] Chizuru Iwasawa:1, Yusuke Hamada:1, Michiko Narita:1, Naoko Kuzumaki:1, Minoru Narita:1
1:Department of Pharmacology, Hoshi University, Japan

 A lot of studies has supported the principal role of mesolimbic dopaminergic system, which originates from the ventral tegmental area and projects mainly to the nucleus accumbens and prefrontal cortex, in producing the rewarding effect of addiction drugs including ethanol (EtOH). Since the molecular target of EtOH to the neuron remain unclear, it is important to identify of cells specifically activated by EtOH in the rewarding system. In the present study, we investigated the characterization of activated cells induced by EtOH in the ventral tegmental area. First of all, activated cells in the ventral tegmental area using FACS were prepared from c-Fos-EGFP-Rp110a (cFos-TRAP) mice, which were chronically treated with EtOH. The activated cells expressed tyrosine hydroxylase (TH) and dopamine transpoter (DAT), indicating the activation of dopaminergic neurons by EtOH. In addition, aldehyde dehydrogenase 1a1 (ALDH1a1) in the activated cell was recognized by chronic treatment with EtOH. It has been reported that ALDH1a1 synthesizes GABA in dopaminergic neurons, and plays an important role in the balanced control of dopamine and GABA co-release. Here we found that chronic treatment with EtOH enhanced ALDH1a1 immunoreactivity in dopaminergic neurons in the ventral tegmental area. These results suggest that chronic treatment with EtOH may increase the expression of ALDH1a1, and subsequently promote GABA synthesis specifically in dopaminergic neurons in the ventral tegmental area. Furthermore, chronic treatment with EtOH may induce drug addiction by an imbalance between dopamine and GABA in dopaminergic neurons of the ventral tegmental area.
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