.1 Of ¦Ã-aminobutyric Acid Transport Protein I (gat1) In The Mouse Central Nervous System In The Physiological Functions Of The Male Reproductive System In Gene Expression And Function Of A Preliminary Study

Na /Cl -dependent GABA transporters play an important role in controlling the concentration of GABA in the synaptic cleft, and thus they control the intensity and duration of synaptic transmission of GABA. In the present study, we found that the activity of GABA transporters was enhanced in the central nervous system (CNS) of mice after 15-min acute ethanol consumption. Ethanol facilitated the translocation of GABA transporter I (GAT1) from intracellular vesicles to plasma membrane and perhaps through an effect on dephosphorylation. Mice pre-injected with a competitive or a noncompetitive antagonist of GAT1 showed high sensitivity to the sedative/hypnotic effects of ethanol. In contrast, transgenic mice overexpressing GAT1 displayed ethanol tolerance, as shown by the righting reflex test. Mice overexpressing GAT1 survived a lethal dose of ethanol (9g/kg, i.p.) longer, maintained locomotor activity longer after a sub-lethal dose (1.75g/kg, i.p.) and exhibited a higher LD 50 than wild-type littermates. These results suggest that GAT1 plays an important role in ethanol tolerance and might be a therapeutic target for alcoholism prevention and treatment.