T. Onaka et al., PRESYNAPTIC ACTIONS OF MORPHINE - BLOCKADE OF CHOLECYSTOKININ-INDUCEDNORADRENALINE RELEASE IN THE RAT SUPRAOPTIC NUCLEUS, Journal of physiology, 482(1), 1995, pp. 69-79
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.