Local injection of pertussis toxin attenuates morphine withdrawal excitation of rat supraoptic nucleus neurones

Morphine inhibits oxytocin neurones via G(i/o)-protein-linked mu-opioid rec eptors. Following chronic morphine administration oxytocin cells develop de pendence, shown by withdrawal excitation after administration of the opioid antagonist, naloxone. Here, inactivation of G(i/o)-proteins by pre-treatme nt of morphine-dependent rats with pertussis toxin injected into the left s upraoptic nucleus reduced withdrawal-induced Fos protein expression within the injected nucleus by 41 +/- 10% compared to the contralateral nucleus, i ndicating that functional G(i/o)-proteins are essential for the development and/or expression of morphine dependence by oxytocin cells in the supraopt ic nucleus. In another group of rats, pertussis toxin did not alter the res ponses to either systemic cholecystokinin administration or systemic hypert onic saline administration, indicating that pertussis toxin does not preven t oxytocin cells from responding to stimuli that are not mediated by G(i/o) -proteins. Finally, pertussis toxin reduced acute morphine inhibition of sy stemic hypertonic saline-induced Fos protein expression in the supraoptic n ucleus, confirming that pertussis toxin effectively inactivates G(i/o)-prot eins in the supraoptic nucleus. Thus, the expression of morphine withdrawal excitation by supraoptic ucleus oxytocin cells requires the functional int egrity of G(i/o)- proteins within the nucleus. (C) 2000 Elsevier Science In c.