The effect of U-50,488H, a kappa-opiate receptor agonist on tolerance to the analgesic and hyperthermic effects of morphine in the rat.
1. The effect of intraperitoneal injections of U-50,488H, a kappa-opiate receptor agonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in male Sprague-Dawley rats. 2. Tolerance was induced by implantation of four morphine pellets during a 3-day period (4/3 schedule) or six morphine pellets during a 7-day period (6/7 schedule). 3. Administration of U-50,488H (25 mg/kg, twice a day for 3 days in 4/3 schedule) or (5, 10 and 20 mg/kg twice a day for 7 days in 6/7 schedule) did not affect the development of tolerance to the pharmacological actions of morphine. 4. It is concluded that activation of kappa-opiate receptors does not modify the development of tolerance to morphine in the rat.
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Matwyshyn
G
G
Ramarao
P
P
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004343:Drug Implants; D004361:Drug Tolerance; D007274:Injections, Intraperitoneal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D000700:Analgesics; D004343:Drug Implants; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine