title: Enhanced binding of nor-binaltorphimine to kappa-opioid receptors in rats dependent on butorphanol.
abstract: Autoradiographic characterization of binding for brain kappa(1) ([(3)H]CI-977) and kappa(2) ([(3)H]bremazocine) in the presence of DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin), DPDPE ([D-Pen(2), D-Pen(5)]-enkephalin), and U-69,593 opioid receptors, in the presence of different concentrations of a selective unlabeled kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI), was performed in rats in which dependence on or withdrawal from butorphanol had been established. Dependence was induced by a 72 hr intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/microl/hr; butorphanol dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 hr following termination (butorphanol withdrawal). IC(50) values from competition studies were estimated by fitting inhibition curves for both kappa(1)- and kappa(2)-opioid receptor assays. In both dependent and withdrawal groups, the IC(50) values obtained against [(3)H]CI-977 or [(3)H]bremazocine with nor-BNI were decreased (ratios of approximately 0.03-0.21 and approximately 0.05-0.42 vs. control, respectively) in brain regions, including frontal cortex, nucleus accumbens, claustrum, dorsal endopiriform nucleus, caudate putamen, parietal cortex, posterior basolateral amygdaloid nucleus, dorsomedial hypothalamus, hippocampus, posterior paraventricular thalamic nucleus, periaqueductal gray, substantia nigra, superficial gray layer of the superior colliculus, ventral tegmental area, and locus coeruleus, compared with control. These results indicate that, in butorphanol-dependent and butorphanol-withdrawal rats, the brain kappa(1)- and kappa(2)-opioid receptors developed a supersensitivity to antagonist binding.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kenro
authors.initials: K
authors.lastname: Sasaki
authors.forename: Younjoo
authors.initials: Y
authors.lastname: Park
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
authors.forename: Robin William
authors.initials: RW
authors.lastname: Rockhold
authors.forename: Ing Kang
authors.initials: IK
authors.lastname: Ho
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002077:Butorphanol / Q000008:administration & dosage / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*
chemical_list: D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D002077:Butorphanol