Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding |
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Authors: | Fan Lir-Wan Tanaka Sachiko Park Younjoo Sasaki Kenro Ma Tangeng Tien Lu-Tai Rockhold Robin William Ho Ing Kang |
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Institution: | Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. |
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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. |
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Keywords: | κ 1-Opioid receptor κ 2-Opioid receptor Butorphanol dependence Butorphanol withdrawal Autoradiography |
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