Elucidating the role of alpha1-containing GABA(A) receptors in ethanol action

摘要: Alcohol (ethanol) has a prominent role in society and is one of the most frequently used abused drugs. Despite pervasive use abuse ethanol, molecular mechanisms ethanol action remain unclear. What well known that intoxication elicits range behavioral effects. These effects likely occur through direct on targets central nervous system. By studying effects, individual can be determined. The function γ-amino butyric acid type A (GABAA) receptors altered by but due to multiple receptor subunits exact GABAA not known. This dissertation focused α1-containing using gene knockin mice with insensitive α1 receptors. In second chapter, were molecularly characterized ethanol-induced assessed. was found mediate acute tolerance motor ataxic ethanol. third involvement induction neuronal activity assessed discrete neuroanatomic regions immediate early c-fos. Specifically, c-fos immunohistochemistry after exposure, chronic finally during withdrawal phase. involved ethanol-mediated dentate gyrus. fourth as physical dependence characterized. Results demonstrated α1-GABAA-Rs play development ataxia. Intriguingly, implicated withdrawal-related hyperexcitability. Knockin more sensitive ethanol's hyperexcitability summary, this further supports GABAA-Rs mechanism action. chiseling away at various components we are beginning elucidate Further elucidation could deepen our understanding behind alcohol alcoholism. may lessened alcoholism potentially cured.