Opioids and rate of positively reinforced behavior: III. Antagonism by the long-lasting kappa antagonist norbinaltorphimine.
Various opioid compounds were examined before and after administration of a 40µg (i.c.v.) dose of norbinaltorphimine (nor-BNI) in rats responding under a fixed ratio 20 schedule of food presentation. At time points ranging from 1 to 133 days after administration of nor-BNI, the dose-effect curve for the kappa opioid bremazocine was shifted to the right of that obtained prior to the administration of nor-BNI. The magnitude of these rightward shifts were somewhat larger at day 14 than day 1, remained unchanged between days 14 and 49, and then declined between days 70 and 133. Nor-BNI also produced large rightward shifts in the dose-effect curves for the kappa opioids U50,488, spiradoline and U69,593, and a small rightward shift in the curve for ethylketocyclazocine. In contrast, nor-BNI did not alter the dose-effect curves for (-)-n-allylnormetazocine, (-)-cyclazocine, nalorphine and the mu opioid morphine. The present findings indicate that the rate-decreasing effects of bremazocine, U50,488, U69,593, spiradoline and ethylketocyclazocine are mediated by agonist activity at the kappa opioid receptor(s). These findings also indicate that nor-BNI is a long-lasting and kappa opioid-selective antagonist that offers a number of advantages over naloxone and naltrexone as a pharmacological tool for examining the kappa opioid-mediated activity of opioid compounds.
Department of Psychology and Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3270, USA.
M.J.
MJ
Picker
C.
C
Mathewson
R.M.
RM
Allen