Dizocilpine (MK-801) blocks tolerance to the analgesic but not to the hyperthermic effect of morphine in the rat.
The effect of dizocilpine (MK-801), an N-methyl-D-aspartate receptor antagonist, on the development of tolerance to the analgesic and hyperthermic effects of morphine was determined in the rat. Tolerance to morphine in male Sprague-Dawley rats was induced by implanting subcutaneously 6 morphine pellets during a 7-day period. Two schedules of intraperitoneal injections of MK-801 were used. In one, the drug was injected once a day, and in the other it was injected twice a day. The doses of MK-801 were 0.03, 0.1 and 0.3 mg/kg. In the treatment once a day, MK-801 blocked the development of tolerance to the analgesic effect of morphine, but there was no dose-dependent effect. In the treatment twice a day, MK-801 produced a dose-dependent inhibition of tolerance to the analgesic effect of morphine. Higher doses of MK-801 produced high mortality. MK-801 given once a day or twice a day failed to affect the tolerance to the hyperthermic effect of morphine. In both schedules of MK-801 treatment, the highest dose of MK-801 resulted in high mortality. It is concluded that MK-801 is selective in blocking the tolerance to the analgesic effect of morphine in the rat.
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois at Chicago 60612.
Matwyshyn
G A
GA
D000698:Analgesia; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005334:Fever / Q000139:chemically induced; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016291:Dizocilpine Maleate; D009020:Morphine