LAUSR

BACKGROUND AND PURPOSE Previous studies showed that glycine receptors (GlyRs) composed of α1 and β subunits are primarily found in spinal cord and brainstem and are potentiated by ethanol (10-100 mM). However, much less is known about the presence, composition, and ethanol sensitivity of GlyRs in higher CNS regions. In the present study, we examined two regions of the brain reward system, the ventral tegmental area (VTA) and the prefrontal cortex (PFC), to determine their GlyR subunit composition and sensitivity to ethanol. EXPERIMENTAL APPROACH To achieve these aims, we used Western blot, immunohistochemistry and electrophysiological techniques in three different models: Wild-type C57BL/6, GlyR α1 knock-in and GlyR α2 knockout mice. KEY RESULTS Similar levels of α and β GlyR subunits were detected in both brain regions, and electrophysiological recordings demonstrated the presence of glycine-activated currents in both areas. The sensitivity of GlyRs to glycine was lower in the PFC compared to VTA. Picrotoxin blocked the glycine-activated current in the PFC and VTA only partially, indicating that both regions express heteromeric αβ receptors. Interestingly, GlyRs in VTA neurons, but not in PFC neurons, were potentiated by ethanol. CONCLUSION AND IMPLICATIONS GlyRs in VTA neurons from WT and α2 KO mice were potentiated by ethanol, but not in neurons from the α1 KI mice, supporting the conclusion that α1 GlyRs are predominantly expressed in the VTA. By contrast, GlyRs in PFC neurons were not potentiated in any of the mouse models studied, suggesting the presence of either α2/α3/α4 rather than α1 GlyR subunits.