Osmotic stress mimics effects of vasopressin on learned behaviour

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Abstract
It has been suggested that arginine vasopressin (AVP) is involved in the retention of learned responses, in addition to its classical physiological functions of water retention and modulation of blood pressure. AVP administered subcutaneously (s.c.), intraventricularly or intracerebrally can prolong extinction of active avoidance behaviour1,2 and can enhance retention in inhibitory (passive) avoidance3–5. These effects have been interpreted as a direct action of AVP on the central nervous system to facilitate memory consolidation3,4. AVP also has facilitatory effects on cognitive function in humans6, and marked deficits in AVP function have been associated with certain types of psychopathology7. Alternative hypotheses for the behavioural actions of AVP have involved motivational constructs such as arousal8, and our recent work has focused on the role of arousal resulting from the activation of peripheral visceral signals in the behavioural effects of peripherally administered AVP9–12. The development of a specific antagonist for AVP13, 1-deaminopenicillamine-2-O-methyl tyrosine arginine vasopressin (dPTyr(Me)AVP), which can reverse the behavioural effects of exogenously administered AVP9–12, has provided a powerful tool for examining the role of AVP in the behavioural responses produced by physiological challenges known to release vasopressin. However, the relationship between the behavioural effects of exogenously administered AVP and the behavioural function of endogenously released AVP has not been evaluated. We report here that a potent peripheral osmotic stimulus, the intraperitoneal (i.p.) injection of hypertonic saline, at doses known to release AVP both centrally14 and peripherally15, will produce behavioural effects similar to those of exogenously administered AVP. Furthermore, the prolongation of active avoidance induced by this osmotic stimulus is reversed by pretreatment with dPTyr(Me)AVP, suggesting that endogenously released AVP may also produce behavioural effects.