Central target for the behavioural effects of vasopressin neuropeptides

The neurohypophysial hormone vasopressin exerts antidiuretic, vasopressor and behavioural effects (for example, facilitation of memory processes). Vasopressin may alter animal behaviour via direct effect on brain processes. Recently, however, it has been suggested that vasopressin acts mainly at peripheral receptor systems and influences behavioural mechanisms by altering visceral afferent signals. We now present data showing that (1) central administration of [Arg8]vasopressin (AVP) and more potently [pGlu, Cyt]AVP(4-8), the desglycinamide derivative of a peptide generated from AVP by brain synaptic membranes, produce the behavioural effect (promotion of passive avoidance behaviour) without the pressor effect; (2) central administration of a vasopressor antagonist blocks the behavioural but not the pressor effect of systemically administered AVP; and (3) [pGlu, Cyt]AVP(4-8) induces the behavioural effect in the absence of the pressor effect. The results indicate that AVP and related peptides affect passive avoidance behaviour by a direct central action and that the structural requirement for activation of central vasopressin receptors differs from that of the peripheral cardiovascular receptors, although both can be blocked by the same vasopressor antagonist.