INHIBITION OF THE VASOPRESSIN-ENHANCING EFFECT ON MEMORY RETRIEVAL AND RELEARNING BY A VASOPRESSIN V-1 RECEPTOR ANTAGONIST IN MICE

We have previously shown that [Arg(8)]vasopressin bilaterally administ ered into the ventral hippocampus of mice at a dose of 0.025 ng/animal 10 min prior to the retention session, improved long-term retrieval p rocesses and relearning of a Go-No-Go visual discrimination task. The purpose of the present study was to determine whether the vasopressin V-1 receptor antagonist, hylenepropionyl(1),O-Me-Tyr(2),Arg(8)]vasopre ssin, d(CH2)(5)Tyr(Me)vasopressin), is able to block the behavioral ef fect of arginine-vasopressin in the ventral hippocampus. We first test ed the effect of three doses of d(CH2)(5)Tyr(Me)vasopressin (0.025, 1, and 6.3 ng/animal) in the same experimental conditions as used for ar ginine-vasopressin. The results showed a dose-dependent deleterious ef fect of the vasopressin V-1 receptor antagonist on retrieval and relea rning, suggesting the involvement of endogenous arginine-vasopressin i n the ventral hippocampus for these memory processes. Second, we teste d the ability of d(CH2)(5)Tyr(Me)vasopressin to block the enhancing ef fect of experimentally administered arginine-vasopressin. The antagoni st was injected at a dose of 0.025 ng, which had no intrinsic effect o n behavior, or at a dose of 1 ng, which had a weak deleterious effect on behavior, followed by administration of 0.025 ng of arginine-vasopr essin. The results showed that even at the weakest dose (0.025 ng), d( CH2)(5)Tyr(Me)vasopressin blocked the enhancing effect of arginine-vas opressin on retrieval and relearning. Thus, as for other behaviors and structures, the antagonist microinjected into the ventral hippocampus prevents the enhancing effect of arginine-vasopressin on long-term re trieval and relearning. However, the exclusive involvement of the vaso pressin V-1 receptors remain to demonstrate vis-a-vis oxytocin recepto rs.