Journal article
Sex differences in opioid antinociception: κ and ‘mixed action’ agonists
Drug and alcohol dependence, Vol.63(3), pp.215-228
2001
Handle:
https://hdl.handle.net/2376/115744
PMID: 11418226
Abstract
A number of investigators have shown that male animals are more sensitive than females to the antinociceptive effects of μ-opioid agonists. The present study was conducted to examine sex differences in opioid antinociception in the rat using agonists known to differ in selectivity for and efficacy at κ- versus μ-receptors. Dose– and time–effect curves were obtained for s.c. U69593, U50488, ethylketazocine, (−)-bremazocine, (−)-pentazocine, butorphanol and nalbuphine on the 50 or 54°C hotplate and warm water tail withdrawal assays; spontaneous locomotor activity was measured 32–52 min post-injection in the same rats. On the hotplate assay, only butorphanol (54°C) and nalbuphine (50°C) were significantly more potent in males than females. On the tail withdrawal assay, all agonists were significantly more potent or efficacious in males than females at one or both temperatures. In contrast, no agonist was consistently more potent in one sex or the other in decreasing locomotor activity. Estrous stage in female rats only slightly influenced opioid effects, accounting for an average of 2.6% of the variance in females’ antinociceptive and locomotor responses to drug (50°C experiment). These results suggest that (1) sex differences in antinociceptive effects of opioids are not μ-receptor-dependent, as they may occur with opioids known to have significant κ-receptor-mediated activity; (2) the mechanisms underlying sex differences in κ-opioid antinociception may be primarily spinal rather than supraspinal; (3) sex differences in antinociceptive effects of opioid agonists are not secondary to sex differences in their sedative effects.
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Details
- Title
- Sex differences in opioid antinociception: κ and ‘mixed action’ agonists
- Creators
- Rebecca M CraftScott A Bernal
- Publication Details
- Drug and alcohol dependence, Vol.63(3), pp.215-228
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier Ireland Ltd
- Identifiers
- 99900547561401842
- Language
- English
- Resource Type
- Journal article