Accepted manuscript
PAG mu opioid receptor activation underlies sex differences in morphine antinociception
Behavioural brain research, Vol.177(1), pp.126-133
2007
Handle:
https://hdl.handle.net/2376/108527
PMCID: PMC1868665
PMID: 17118467
Abstract
Given the findings that (1) systemic opioid antinociception varies by estrous stage in females and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle and (2) examining systemic morphine antinociception in males versus females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3–10
μg), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females’ response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist β-funaltrexamine (β-FNA) into the vPAG shifted the systemic morphine dose–effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine.
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Details
- Title
- PAG mu opioid receptor activation underlies sex differences in morphine antinociception
- Creators
- Scott A Bernal - Department of Psychology, Washington State University, Pullman, WA 99164-4820, United StatesMichael M Morgan - Department of Psychology, Washington State University, Vancouver, WA 98686, United StatesRebecca M Craft - Department of Psychology, Washington State University, Pullman, WA 99164-4820, United States
- Publication Details
- Behavioural brain research, Vol.177(1), pp.126-133
- Academic Unit
- Psychology, Department of
- Publisher
- Elsevier B.V
- Identifiers
- 99900546862201842
- Language
- English
- Resource Type
- Accepted manuscript