Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice

Background and Purpose Glycine receptors composed of alpha 1 and beta subunits are primarily found in the 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 these receptors in higher CNS regions. Here, we examined two regions of the brain reward system, the ventral tegmental area (VTA) and the prefrontal cortex (PFC), to determine their glycine receptor subunit composition and sensitivity to ethanol. Experimental Approach We used Western blot, immunohistochemistry and electrophysiological techniques in three different models: wild-type C57BL/6, glycine receptor subunit alpha 1 knock-in and glycine receptor subunit alpha 2 knockout mice. Key Results Similar levels of alpha and beta receptor subunits were detected in both brain regions, and electrophysiological recordings demonstrated the presence of glycine-activated currents in both areas. Sensitivity of glycine receptors to glycine was lower in the PFC compared with VTA. Picrotoxin only partly blocked the glycine-activated current in the PFC and VTA, indicating that both regions express heteromeric alpha beta receptors. Glycine receptors in VTA neurons, but not in PFC neurons, were potentiated by ethanol. Conclusion and Implications Glycine receptors in VTA neurons from WT and alpha 2 KO mice were potentiated by ethanol, but not in neurons from the alpha 1 KI mice, supporting the conclusion that alpha 1 glycine receptors are predominantly expressed in the VTA. By contrast, glycine receptors in PFC neurons were not potentiated in any of the mouse models studied, suggesting the presence of alpha 2/alpha 3/alpha 4, rather than alpha 1 glycine receptor subunits.