OPIOID ANTAGONIST DIPRENORPHINE MICROINJECTED INTO PARABRACHIAL NUCLEUS SELECTIVELY INHIBITS VASOPRESSIN RESPONSE TO HYPOVOLEMIC STIMULI INTHE RAT

Subcutaneous injection of the potent, nonselective opioid antagonist d iprenorphine inhibits the vasopressin response to acute hypovolemia. T o determine if this inhibition is due to antagonism of opioid receptor s in brain pathways that mediate volume control, we determined the vas opressin response to different stimuli when diprenorphine or other opi ates were injected into the cerebral ventricles, the nucleus tractus s olitarius (NTS), or the lateral parabrachial nucleus (PBN) of rats. We found that the vasopressin response to hypovolemia was inhibited by i njection of diprenorphine into the cerebral ventricles at a dose too l ow to be effective when given subcutaneously. This response also was i nhibited when a 20-fold lower dose of diprenorphine was injected into the PBN but not when it was injected into the NTS. The inhibitory effe ct of diprenorphine in the PBN was not attributable to a decrease in o smotic or hypovolemic stimulation and did not occur with osmotic or hy potensive stimuli. Injecting the PBN with equimolar doses of the mu an tagonist naloxone, the delta antagonist ICI-154,129 or the kappa-1 ago nist U-50,488H had no effect on basal or volume-stimulated vasopressin . We conclude that the inhibition of vasopressin by diprenorphine is d ue partially to action at a novel class of opioid receptors that trans mit volume stimuli through the PBN.