Kappa receptor mediated opioid dependence in rhesus monkeys.
The kappa receptor-selective agonist U-50, 488 was administered chronically to rhesus monkeys. Tolerance developed to the overt behavioral effects of U-50,488 without cross-tolerance to morphine. Withdrawal behaviors produced by deprivation, naloxone or quadazocine administration in U-50, 488-dependent monkeys consisted of hyperactivity, excessive grooming, and yawning. The syndrome was suppressed in a dose-related manner by a kappa agonist, ethylketazocine, but not by doses of morphine that suppressed its own withdrawal. The mu-selective antagonist, beta-funaltrexamine, at doses which are active in morphine-dependent monkeys, did not precipitate withdrawal in U50, 488-dependent monkeys. Dependence, which is the result of activity at the kappa receptor, was distinct from morphine dependence.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D008253:Macaca mulatta / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000503:physiopathology*
D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer