Artículo de revista
Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice
Fecha
2021Registro en:
Br J Pharmacol. 2021;178:4691–4707.
10.1111/bph.15649
Autor
Araya, Aníbal
Gallegos, Scarlet
Viveros, Rodrigo
San Martín, Loreto
Muñoz, Braulio
Harvey, Robert
Zeilhofer, Hanns U.
Aguallo, Luis G.
Institución
Resumen
Background and Purpose: Glycine receptors composed of α1 and β 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 α1 knock-in and glycine receptor subunit α2 knockout mice.
Key Results: Similar levels of α and β receptor subunits were detected in both brain
regions, and electrophysiological recordings demonstrated the presence of glycineactivated
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 αβ
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 α2 KO
mice were potentiated by ethanol, but not in neurons from the α1 KI mice,
supporting the conclusion that α1 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 α2/α3/α4, rather than α1
glycine receptor subunits.