title: Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.
abstract: The present study examines the degree and distribution of alterations in the expression of kappa-opioid receptor subtypes using a model of chronic intracerebroventricular (i.c.v.) infusion of butorphanol. Autoradiographic characterization of binding for brain kappa(1) ([3H]CI-977)-, kappa(2) ([3H]bremazocine in the presence of DAMGO, DPDPE, and U-69,593)- and total kappa ([3H]bremazocine in the presence of only DAMGO and DPDPE)-opioid receptors was performed. Dependence was induced by a 72 h i.c.v. infusion with butorphanol (26 nmol/microl per hour) (butorphanol-dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 h following termination (butorphanol-withdrawal). During both dependence and withdrawal phases, the binding signals for both kappa(1)- and kappa(2)-opioid receptors were significantly increased in certain regions, with especially marked increases in the frontal cortex, nucleus accumbens, parietal cortex, dorsomedial hypothalamus, ventral tegmental area and locus coeruleus. In contrast, a highly specific decrease in kappa(2)-, but increase in kappa(1)-, opioid receptor binding was noted in the hippocampus of rats in both butorphanol-dependent and-withdrawal groups. Therefore, alterations in kappa(1)- and kappa(2)-opioid receptors in the hippocampus may be differently involved in both adaptation to and recovery from chronic exposure to a mixed agonist/antagonist opioid analgesic. These results further illustrate the regional distribution of changes in binding characteristics of rat brain kappa(1)- and kappa(2)-opioid receptor subtypes in an established model of butorphanol dependence and withdrawal.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Lir-Wan
authors.initials: LW
authors.lastname: Fan
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Younjoo
authors.initials: Y
authors.lastname: Park
authors.forename: Kenro
authors.initials: K
authors.lastname: Sasaki
authors.forename: Tangeng
authors.initials: T
authors.lastname: Ma
authors.forename: Lu-Tai
authors.initials: LT
authors.lastname: Tien
authors.forename: Robin William
authors.initials: RW
authors.lastname: Rockhold
authors.forename: Ing Kang
authors.initials: IK
authors.lastname: Ho
mesh_terms: D000818:Animals; D002077:Butorphanol / Q000009:adverse effects*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009293:Opioid-Related Disorders / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D017473:Receptors, Opioid, kappa; C108819:kappa(2) opioid receptor; D002077:Butorphanol