sub-chronic treatment with ethanol induces a cross-tolerance to several WIN-induced behaviors including its antinociceptive effects (Pava et al., 2012), and it is possible that this reduction in CB1 function may be mediated by GASP1. Alternatively, cross-tolerance between the analgesic effects of μ-opioid and CB1 receptor activation is mediated by receptor desensitization that involves signaling through Gαz, and mice with a knockdown of Gαz do not develop this cross-tolerance (Garzón et al., 2009). As a consequence, the ethanol-induced knockdown of CB1 function may be facilitated through Gαz signaling.
