Journal article
Intermediate efficacy mu opioids: examination of their morphine-like stimulus effects and response rate-decreasing effects in morphine-tolerant rats
The Journal of pharmacology and experimental therapeutics, Vol.263(2), pp.668-681
11/1992
Handle:
https://hdl.handle.net/2376/114456
PMID: 1331411
Abstract
The present study examined the effects of morphine, the intermediate efficacy mu opioids (-)-pentazocine, (-)-metazocine, proxorphan, levallorphan, (-)-NANMY (N-allylnormetazocine) and (-)-cyclazocine, and the mu antagonist naloxone 1) in rats responding under a FR (fixed-ratio) 30 schedule before, during and after a chronic morphine regimen, and 2) in rats trained to discriminate 10.0 [10-MS (morphine sulfate)] or 3.0 mg/kg (3-MS) of morphine from saline. Under the FR30 schedule, chronic administration of morphine produced tolerance to morphine's rate-decreasing effects and conferred cross-tolerance to (-)-metazocine, proxorphan and (-)-pentazocine. However, the effects of these intermediate efficacy mu opioids could be differentiated from those of morphine on the basis of their 1) shallow dose-effect curves, and 2) large differences in the degree to which tolerance developed in individual rats. In the drug discrimination procedure, (-)-metazocine, proxorphan and (-)-pentazocine produced high levels of substitution for the 3-MS stimulus and intermediate levels for the 10-MS stimulus. In contrast to the pattern of substitution observed with morphine in the 10-MS group, the effects of these drugs were characterized by 1) shallow dose-effect curves, 2) large individual differences in the lowest dose of each drug that substituted completely for the 10-MS stimulus and 3) the failure to obtain complete substitution for the 10-MS stimulus in all of the rats tested. The behavioral profile obtained with the intermediate efficacy mu opioids (-)-NANM, levallorphan and (-)-cyclazocine was indicative of opioids with intrinsic efficacy lower than that of (-)-pentazocine, (-)-metazocine and proxorphan. Under the FR30 schedule, chronic administration of morphine produced an enhanced sensitivity to the rate-decreasing effects of (-)-NANM and levallorphan but not (-)-cyclazocine. In the drug discrimination procedure, (-)-NANM, levallorphan and (-)-cyclazocine produced high levels of substitution for the 3-MS stimulus and low levels for the 10-MS stimulus. Like naloxone, these drugs produced a dose-related attenuation of the 10-MS stimulus. The results of the present study suggest that the relative order of intrinsic efficacy among the opioids tested is: morphine > (-)-metazocine = (-)-pentazocine = proxorphan > (-)-cyclazocine = levallorphan = (-)-NANM > naloxone.
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Details
- Title
- Intermediate efficacy mu opioids: examination of their morphine-like stimulus effects and response rate-decreasing effects in morphine-tolerant rats
- Creators
- M J Picker - Department of Psychology, University of North Carolina, Chapel HillR M CraftS S NegusK R PowellS R MattoxS R JonesB K HargroveL A Dykstra
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.263(2), pp.668-681
- Academic Unit
- Psychology, Department of
- Publisher
- United States
- Grant note
- KO5DA00033 / NIDA NIH HHS DA02749 / NIDA NIH HHS DA07327 / NIDA NIH HHS
- Identifiers
- 99900548345901842
- Language
- English
- Resource Type
- Journal article