Intracerebroventricular application of a vasopressin antagonist peptide prevents the behavioral actions of vasopressin.

Three experiments were conducted to test the hypothesis that the memory-improving properties of peripherally-applied vasopressin (AVP) were related to its aversive (i.e. arousing) actions. The memory effects of AVP were observed in a one-trial food-finding task where non-deprived rats were briefly exposed to a large open field that contained an alcove in which a high-incentive familiar food reward (sweetened milk) was freely available. AVP injections immediately upon removal from the open-field produced faster latencies to refind the alcove (compared to vehicle controls) when tested 48 h later. The aversive actions of AVP were demonstrated in two behavioral assays: (1) a conditioned taste aversion test in which rats learned to avoid a preferred saccharin solution after it had been paired with injections of AVP; and (2) a conditioned place test in which rats learned to avoid a distinctive environment associated with AVP administration. Both the memory and aversive responses to AVP were prevented, in a dose-dependent manner, by immediate pretreatment with intracerebroventricular infusions of the pressor antagonist analog 1-deaminopenicillamine-2-(O-methyl)-tyrosine AVP. The large antagonist doses required to block AVP's behavioral effects suggest that the critical site of action may be far removed from the lateral ventricles. The possibility that AVP-induced improvements in memory result from peripheral arousing actions is discussed.