title: Binding characteristics of [3H]SCH 23390 in spinal cord and discrete brain regions of kappa-opiate tolerant-dependent and abstinent rats.
abstract: The effects of chronic administration of U-50,488H, a highly selective kappa-opiate receptor agonist, and its subsequent withdrawal were determined. The binding characteristics of [3H]SCH 23390 to dopamine D1 receptors were investigated on membranes of rat spinal cord and in discrete brain regions. Male Sprague-Dawley rats received U-50,488H (25 mg/kg) intraperitoneally twice a day for 4 days. Animals serving as controls received only vehicle. Two different treatment schedules were used. In one, rats were injected with U-40,588H on day 5 and were sacrificed 1 h later (tolerant-dependent rats). In another, the rats were sacrificed 16 h after the last injection of U-50,488H (abstinent rats). Chronic administration of U-50,488H resulted in the development of tolerance to its analgesic effect, as demonstrated by the decreased response to a challenge dose of U-50,488H compared to vehicle-injected rats. The binding characteristics (Bmax and Kd values) of [3H]SCH 23390 were unaffected in spinal cord and other regions of brain of tolerant-dependent rats. In U-50,488H-abstinent rats, Bmax values of [3H]SCH 23390 were increased in hypothalamic and striatal membranes, but Kd values were unaffected. These results suggest that, in U-50,488H-abstinent rats, dopamine D1 receptors are up-regulated in hypothalamus and striatum.
authors.affiliation: Department of Pharmacodynamics, University of Illinois, Chicago Health Sciences Center.
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.forename: P
authors.initials: P
authors.lastname: Ramarao
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004361:Drug Tolerance; D007700:Kinetics; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism
chemical_list: D000700:Analgesics; D001552:Benzazepines; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer