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 administered 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 processes 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, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]vasopressin, d(CH2)(5)Tyr(Me)vasopressin), is able to block the behavioral effect of arginine-vasopressin in the ventral hippocampus. We first tested 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 arginine-vasopressin. The results showed a dose-dependent deleterious effect of the vasopressin V-1 receptor antagonist on retrieval and relearning, suggesting the involvement of endogenous arginine-vasopressin in the ventral hippocampus for these memory processes. Second, we tested the ability of d(CH2)(5)Tyr(Me)vasopressin to block the enhancing effect of experimentally administered arginine-vasopressin. The antagonist was injected at a dose of 0.025 ng, which had no intrinsic effect on 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-vasopressin. The results showed that even at the weakest dose (0.025 ng), d(CH2)(5)Tyr(Me)vasopressin blocked the enhancing effect of arginine-vasopressin 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 retrieval and relearning. However, the exclusive involvement of the vasopressin V-1 receptors remain to demonstrate vis-a-vis oxytocin receptors.