Regional c-Fos expression induced by peripheral oxytocin administration is prevented by the vasopressin 1A receptor antagonist SR49059

Peripherally administered oxytocin induces a wide range of behavioural and physiological effects that are thought to be mediated by the oxytocin receptor (OTR). However, oxytocin also has considerable affinity for the vasopressin 1A receptor (V_1AR), such that various oxytocinergic effects may in fact be mediated by the V_1AR rather than the OTR. Here we used c-Fos immunohistochemistry to determine the extent to which the regional pattern of neuronal activation produced by peripheral oxytocin involves the V_1AR. Male Wistar rats were administered oxytocin (1 mg/kg, IP) alone, or following pre-treatment with the V_1AR antagonist SR49059 (1 mg/kg, IP), and were assessed for locomotor activity changes and for c-Fos expression across a number of brain regions. Oxytocin reduced the distance travelled by rats during a 70 min test session, and this inhibitory behavioural effect was prevented by SR49059. Consistent with previous reports, oxytocin increased c-Fos expression in a number of brain regions. In several of these regions—the supraoptic and paraventricular (PVN) nuclei of the hypothalamus, locus coeruleus and nucleus of the solitary tract—the c-Fos response was prevented by SR49059 pre-treatment. Notably, SR49059 inhibited the c-Fos activation in oxytocin-synthesising magnocellular neurons in the PVN. However, c-Fos expression in the central amygdala to oxytocin was unaffected by SR49059. The current findings add to an increasing body of research suggesting that many of the functional effects of oxytocin may be V_1AR mediated.