Vasopressor receptor antagonist prevents behavioural effects of vasopressin

Abstract

The antidiuretic hormone vasopressin¹ also has a direct vasoconstrictor effect on the smooth muscles of the vascular system2. This may be physiologically significant³, but higher doses of the hormone are required in conscious subjects than when the autonomie nervous system is depressed by anaesthesia or ganglionic blocking agents². Vasopressin may also function as a releaser of corticotropin^4,5, in the maintenance of learned avoidance behaviours and in memory consolidation^6–8. Although these functions are controversial^9–11, it is of interest that corticotropin^12,13 and other peptides cleaved from the propiocortin14 precursor also influence avoidance behaviours¹³. Here, we have examined a highly potent peptide analogue¹⁵ of arginine vasopressin (AVP) for its ability to antagonize the pressor and behavioural responses to AVP in conscious rats. Our results indicate that doses of AVP which prolong extinction of active avoidance behaviour for several hours after subcutaneous injection^8,13,16, also produce early pressor responses. Conversely, we also find that doses of the antagonist peptide, 1–deaminopenicillamine, 2–(O-methyl)tyrosine AVP (dPTyr-(Me)AVP), which can prevent the pressor response¹⁵, also abolish the effects of subcutaneously injected AVP on prolongation of extinction. This blockade indicates that signals from peripheral visceral sources may have an important role in the subsequent behavioural changes, and suggests that the receptors at which AVP elicits its pressor effect are similar to those leading to its behavioural action.