Crosstolerance between butorphanol and morphine in rats.
To investigate the antinociceptive effects of morphine and U-50,488 after continuous administration with butorphanol, rats were intracerebroventricularly (ICV) infused with butorphanol (26 nmol/microliters/h) through osmotic minipumps for 3 days. Six hours after termination of infusion, the rats were challenged with different doses of morphine or U-50,488. Antinociceptive effects, as assessed by tail-flick and acetic acid writing tests, were measured 15 min after challenge. Development of crosstolerance to morphine was evident in butorphanol-infused animals. The study also revealed that crosstolerance to butorphanol developed in continuously ICV morphine-infused animals. Continuous ICV infusion with butorphanol produced a marked rightward shift of the antinociceptive dose-response curve resulting from U-50,488 challenge. These results showed that there is an antinociceptive crosstolerance between butorphanol and morphine, and crosstolerance to U-50,488 developed in continuously butorphanol-infused animals. The present data suggested that chronic ICV treatment with high doses of butorphanol can lead to desensitization of the antinociceptive systems mediated through the central kappa as well as mu receptors in rats.
Feng
Y Z
YZ
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Narita
M
M
Tseng
Y T
YT
Hoskins
B
B
Ho
I K
IK
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002077:Butorphanol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D002077:Butorphanol