Acute Ethanol Exposure Inhibits GABA Uptake in Embryonic Chicken Retina

Abstract

Abstract GABA is the major inhibitory amino acid in the central nervous system (CNS), and its homeostasis is crucial for inhibitory/excitatory balance. Its reuptake is mediated by GABA transporters, including type 1 (GAT-1), a high-affinity GABA plasma membrane transporter. Ethanol (EtOH) consumption enhances GABA inhibitory effects; however, the impact of acute EtOH exposure on GABAergic function during development remains to be understood. Therefore, we aimed to evaluate whether acute EtOH exposure modulates GABA transport in chicken retina, a well-established model for investigating neurochemical studies. GABA transporter is functional from the onset of synaptogenesis (embryonic day—E11) to E16 in chicken retina. A dose–response curve in E11 suggested that exposure to 0.1% EtOH reduced GABA uptake. This effect was not related to cell death, as cytotoxicity assays performed through lactate dehydrogenase (LDH) release showed no significant changes in E11. Additionally, inhibition of PKA and PKC pathways reversed the EtOH 0.1%-effect, suggesting the involvement of these kinases in regulating GABA transport. In contrast, Ifenprodil treatment did not alter the inhibitory effect of EtOH on GABA uptake, suggesting that GluN2B-containing NMDA receptors are not major contributors to this response. Our findings demonstrate that GABA uptake through GAT-1 during synaptogenesis may play a role in the synaptic circuitry of avian retina. Acute exposure to 0.1% EtOH did not significantly alter GABA uptake at E16 as was indicated in E11, suggesting an age-dependent effect of EtOH on retinal development, independent of cell death. These results support the hypothesis that acute EtOH exposure modulates GABA transport during retinal development, with the involvement of PKA and PKC pathways in this response.