EFFECTS OF A SINGLE ADMINISTRATION OF OXYTOCIN OR VASOPRESSIN AND THEIR INTERACTIONS WITH 2 SELECTIVE RECEPTOR ANTAGONISTS ON MEMORY STORAGE IN MICE

The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have be en thought to play a significant role in behavioral regulation in gene ral and in learning and memory in particular. Experimental evidence su ggests that AVP improves, and OT impairs, learning and memory. The pre sent paper investigates the posttraining effects of OT and of an OT re ceptor antagonist, and their interaction, on memory storage in mice. A dditional studies were conducted to determine the specificity of the i nteraction between OT and its receptors. Male Swiss mice were tested 4 8 h after training in a one-trial step-through inhibitory avoidance ta sk. Immediate posttraining subcutaneous injection of OT (0.01, 0.03, 0 .10, 0.30, and 1.00 mu g/kg) impaired retention performance. The dose- response curve showed a U-shaped form, with a significant impairment s een at doses of 0.10 and 0.30 mu g/kg of OT. In contrast, the immediat e posttraining administration of the putative oxytocin receptor antago nist d(CH2)(5)[Tyr(Me)(2), Thr(4), Thy-NH29]OVT(AOT, 0.03, 0.10, 0.30, and 1.00 mu g/kg) significantly enhanced retention performance. The d ose-response curve was an inverted ''U'' in this range of doses. Howev er, of the doses tested, only 0.30 mu g/kg was effective. Neither OT n or AOT affected response latencies in mice not given the footshock on the training trial, indicating that the actions of both treatments on retention performance were not due to nonspecific proactive effects on response latencies. Neither the imparing effects of OT (0.10 mu g/kg) nor the enhancing effects of AOT (0.30 mu g/kg) were seen when the tr aining-treatment interval was 180 min, suggesting that both treatments influenced the storage of recently acquired information. The effects of OT (0.10 mu g/kg) on retention were prevented by AOT (0.03 mu g/kg) administered immediately after training, but 10 min prior to oxytocin treatment. This dose of antagonist did not affect retention by itself , either under the standard experimental conditions or in mice trained with a lower level of footshock. On the contrary, OT (0.10 mu g/kg) i mpaired retention in mice pretreated with the V-1a vasopressin recepto r antagonist d(CH2)(5)[Tyr(Me)(2)]Avp (0.01 mu g/kg), which, however, was able to prevent the enhancement of retention induced by posttraini ng administration of AVP (0.03 mu g/kg). Finally, the effects of AVP ( 0.03 mu g/kg) on retention were not prevented by AOT (0.03 mu g/kg). C onsidered together, these findings suggest that the impairment of rete ntion of an inhibitory avoidance response in mice induced by posttrain ing oxytocin is probably due to an interaction of the neuropeptide wit h specific receptors. (C) 1998 Academic Press.