AN ANXIOLYTIC ACTION OF OXYTOCIN IS ENHANCED BY ESTROGEN IN THE MOUSE

The established role of oxytocin (OT) in facilitation of steroid-modul ated reproductive and affiliative behaviors led to the speculation tha t it may have anxiolytic actions under certain hormonal conditions. NM -Swiss mice were tested for responsiveness to OT in two behavioral tes ts of anxiety, the holeboard apparatus and elevated plus-maze. Dose-re sponse assessment indicated that 3 mg/kg was the optimal dose for peri pherally administered (IF) OT on the elevated plus-maze. There were no consistent effects at any dose on the holeboard apparatus. In ovariec tomized mice pretreated with estradiol (E(2)), peripherally administer ed OT increased the number of entrances onto the open arms, as well as the amount of time on the open arms compared to other groups (ANOVA; p < 0.05). There was little to no effect of OT in ovariectomized anima ls not pretreated with E(2). When OT was administered intracerebrovent ricularly (ICV), there was an increase in entrances and time on the op en arms compared to that of females infused with arginine vasopressin (AVP). This increase was apparent in ovariectomized females, but was f urther enhanced in those pretreated with E(2) (ANOVA; p < 0.05). In co ntrast, the combination of E(2) pretreatment and ICV AVP decreased the number of entrances and time spent on the open arms of the elevated p lus-maze compared to those receiving OT, suggesting an estrogen-modula ted anxiogenic action of AVP. Analyses of I-[125]-OVTA binding density indicated a significant increase in binding density in the lateral se ptum of E(2)-treated females compared to OIL-treated controls (ANOVA; p < 0.05). There was no effect of E(2) treatment on I-[125]-OVTA bindi ng density in the amygdala or ventromedial nucleus of the hypothalamus . Taken together, these data indicate that OT exerts an anxiolytic act ion that is enhanced in the presence of circulating estrogen. This beh avioral effect may be mediated by estrogen-induced increases in OT bin ding density in the lateral septum and may be important to the facilit ation of social interactions. Copyright (C) 1996 Elsevier Science Inc.