Involvement of kappa-opioid receptors in opioid dependence/withdrawal: studies using butorphanol.
The dependence liability of a class of opioid agonist/antagonist analgesics, e.g. pentazocine, butorphanol, and buprenorphine, is widely recognized. However, the relative involvement of mu-, delta-, and kappa-opioid receptors mediating physical dependence on these compounds is not completely known. In the present study, butorphanol dependence was produced by continuous intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/h) for 3 days in male Sprague-Dawley rats. Nor-binaltorphimine, a long-acting kappa-opioid receptor antagonist, and naloxone, a nonspecific antagonist, were administered i.c.v. to precipitate withdrawal in butorphanol-dependent animals, so as to investigate the involvement of central kappa-opioid receptors in opioid dependence. ED50 ratios (naloxone/nor-binaltorphimine) for eliciting withdrawal signs were: teeth-chattering (1.25), yawning (2.13), and ejaculation (0.72). Our data indicate that nor-binaltorphimine precipitated withdrawal behaviors similar to those precipitated by naloxone. It appears that central kappa-opioid receptors may play a major role in the development of butorphanol dependence in rats.
Jaw
S P
SP
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Makimura
M
M
Oh
K W
KW
Hoskins
B
B
Ho
I K
IK
D000818:Animals; D002077:Butorphanol; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000209:etiology*
D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D002077:Butorphanol