Effect of chronic administration of U-50,488H, a kappa-opioid receptor agonist, on central dopamine D2 receptors of the rat.
The effect of U-50,488H, a kappa-opiate agonist, induced tolerance and abstinence on the characteristics of dopamine D2 receptors of brain regions and spinal cord was determined in the rat. Male Sprague-Dawley rats were injected with U-50,488H (25 mg/kg i.p) or its vehicle twice a day for 4 days. This procedure resulted in the development of tolerance to the analgesic activity of U-50,488H. The binding characteristics (Bmax and Kd values) of [3H]spiroperidol to dopamine D2 receptors were determined in discrete brain regions (hypothalamus, hippocampus, cortex, pons and medulla, midbrain, corpus striatum and amygdala) and spinal cord of U-50,488H-tolerant and -abstinent rats. Rats labeled as tolerant to U-50,488H were injected with U-50,488H on day 5 and killed 1 h later, whereas those labeled abstinent were killed on day 5 without the injection of the drug. Vehicle-injected rats served as controls. [3H]Spiroperidol bound to brain regions and spinal cord membranes at a single high affinity site. The Bmax and Kd values of [3H]spiroperidol in brain regions and spinal cord of U-50,488H-tolerant and abstinent rats did not differ from their respective vehicle-injected controls. The behavioral responses (total distance travelled, horizontal activity, movement time, total number of movements, number of stereotypic movements, stereotypic time and rest time) to different doses of a selective dopamine D2 receptor agonist, 2-bromo-alpha-ergocryptine (bromocriptine) were also determined in rats treated chronically with U-50,488H.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacodynamics (M/C 865), University of Illinois, Chicago 60612.
Veeranna
P L
PL
Reddy
H N
HN
Bhargava
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001971:Bromocriptine / Q000494:pharmacology; D004361:Drug Tolerance; D008297:Male; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D015854:Up-Regulation
D000700:Analgesics; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D017473:Receptors, Opioid, kappa; D001971:Bromocriptine; D013134:Spiperone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer