At last, we show that, in male mice, antalarmin abolishes morphine-induced firing in neurons co-expressing OXY and AVP, but not in neurons expressing only AVP, thereby suggesting a sex-dependent mechanism of action involving CRF1 receptors and oxytocinergic neurons of the PVN.

Then, we replicate these results using the CRF1 genetic mouse model, and show that CRF1 receptor-deficiency prevents morphine-induced sociability deficits and firing of PVN neurons in a gene expression-dependent manner.

In parallel, we show that antalarmin also eliminates morphine-induced firing of PVN neurons in a sex-dependent manner.

First of all, we show that per os administration of the CRF1 receptor antagonist antalarmin completely abolishes sociability deficits induced by morphine, although exclusively in male mice.