PRESYNAPTIC ACTIONS OF MORPHINE - BLOCKADE OF CHOLECYSTOKININ-INDUCEDNORADRENALINE RELEASE IN THE RAT SUPRAOPTIC NUCLEUS

1. This study aimed to establish the site at which morphine acts to in hibit oxytocin release in response to peripheral administration of cho lecystokinin (CCK). 2. Conscious rats were given morphine or vehicle f ollowed by CCK or vehicle (I.V.). Fos immunoreactivity was apparent 90 min after CCK injection in the supraoptic nucleus of vehicle- but not morphine-pretreated animals. 3. In the dorsomedial (C2/A2) and the ve ntrolateral (C1/A1) regions of the brainstem, about half of the cells immunoreactive for tyrosine hydroxylase (TH) expressed Fos-like protei n after CCK injection. In the C2/A2 region, 20% of the Fos-positive ce lls also showed TH immunoreactivity, whereas in the C1/A1 region 68% d id so. Morphine treatment did not significantly change the number of c ells expressing Fos immunoreactivity, or the percentage of TH-positive cells expressing Fos-like protein. 4. Amine release was measured in t he supraoptic nucleus of urethane-anaesthetized rats using a microdial ysis probe. An I.V. injection of CCK increased the concentrations in t he dialysate of noradrenaline and serotonin, but not of either adrenal ine or dopamine. Pretreatment with morphine (I.V.) blocked the effects of CCK in a naloxone-reversible manner. 5. Inclusion of morphine in t he dialysate also blocked the increase in noradrenaline and serotonin in response to CCK in a naloxone-reversible manner. 6. These observati ons indicate that morphine acts near or within the supraoptic nucleus to block CCK-evoked noradrenaline release presynaptically. This presyn aptic action of morphine may be a cause of the blockade of oxytocin re lease after CCK.