Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.

Article Details

Citation

Fan LW, Tanaka S, Park Y, Sasaki K, Ma T, Tien LT, Rockhold RW, Ho IK

Butorphanol dependence and withdrawal decrease hippocampal kappa 2-opioid receptor binding.

Brain Res. 2002 Dec 27;958(2):277-90.

PubMed ID
12470863 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ButorphanolDelta-type opioid receptorProteinHumans
Yes
Agonist
Details
ButorphanolKappa-type opioid receptorProteinHumans
Yes
Agonist
Details
ButorphanolMu-type opioid receptorProteinHumans
Yes
Antagonist
Details