NOR-BINALTORPHIMINE PRECIPITATES WITHDRAWAL AND EXCITATORY AMINO-ACIDRELEASE IN THE LOCUS-CERULEUS OF BUTORPHANOL - BUT NOT MORPHINE-DEPENDENT RATS

The relative involvement of kappa opioid receptors in the mediation of behavioral and neurochemical responses to withdrawal from chronic dru g treatment with the opioid analgesic butorphanol was studied using in vivo microdialysis to detail extracellular fluid concentrations of gl utamate and aspartate within the locus ceruleus. Sprague-Dawley rats w ere rendered opioid dependent after 3 days of intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/mu l/hr) or morphine (26 nmo l/mu l/hr) and after i.c.v. infusion of saline vehicle (1 mu l/hr). Ac ute withdrawal was precipitated by i.c.v. injection of the selective k appa opioid receptor antagonist nor-binaltorphimine (48 nmol/5 mu l) a fter the 3-day period of infusion. Behavioral signs of withdrawal were detected after nor-binaltorphimine only in butorphanol-dependent rats . Basal levels of glutamate and aspartate were not different between t reatment groups. Nor-binaltorphimine in the butorphanol-dependent rats increased glutamate to 227% and aspartate to 158% in the initial 15-m in sample (P < 0.01). Nor-binaltorphimine did not increase glutamate o r aspartate concentrations in the morphine-dependent or saline-treated groups. These results indicate a significantly greater participation of kappa opioid receptors in the development of butorphanol, rather th an morphine, dependence and identify a differential neurochemical resp onse to butorphanol withdrawal within a defined brain region, the locu s ceruleus.