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Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice

Abstract

Rationale

Evidence based on clinical and experimental animal studies indicates that adolescent social deprivation influences alcohol consumption in a sex-dependent manner, perhaps by influencing stress responses. However, the mechanisms underlying the interaction between these phenomena remain to be elucidated. Since the μ-opioid receptor (MOP) has been reported to have key roles in social stress responses as well as the reinforcing/addictive effects of ethanol, MOP is a candidate molecule that may link adolescent social deprivation and subsequent alterations in alcohol consumption.

Objectives

To evaluate the involvement of MOP and social isolation-induced changes in alcohol consumption, as well as the effect of sex differences on responses to social isolation, alcohol consumption was assessed using a two-bottle home-cage consumption procedure (8 % ethanol vs. water) in MOP knockout (MOP-KO) and wild type (WT) mice of both sexes exposed to adolescent social deprivation or reared socially.

Results

Isolation rearing had no effects upon alcohol consumption of WT mice, whereas it significantly altered alcohol consumption in both male and female MOP-KO mice. Interestingly, social isolation affected ethanol consumption differently in male and female mice. Ethanol consumption was increased in male MOP-KO mice, but decreased in female MOP-KO mice, by isolation rearing.

Conclusion

These results indicate that disturbances of MOP function influence the effects of isolation rearing on ethanol consumption in a sex-dependent manner. Consequently, this suggests the possibility that genetic variation that influences MOP function may have differential roles in alcoholism in men and women, and alcoholism treatments that target MOP function may be differentially effective in males and females.

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Acknowledgments

This work was supported by a Japan Society for the Promotion Science (JSPS) KAKENHI Grant-in-Aid for JSPS Fellows (254961); by an Intramural Research Grant for Collaboration on Special Project Research from IRIDeS, Tohoku University, JSPS Grant-in-Aid for scientific research on innovative areas (24116007); by a Grant-in-Aid for Health and Labour Science Research (Research on Pharmaceutical and Medical Safety) from MHLW of Japan; by a Grant from the Ministry of Health, Labour and Welfare of Japan; by the Global COE Program (Basic & Translational Research Center for Global Brain Science) from MEXT of Japan; and through funding from the Intramural Research Program of the National Institute on Drug Abuse, NIH/DHHS, USA (GRU and FSH).

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Correspondence to Ichiro Sora.

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Moriya, Y., Kasahara, Y., Hall, F.S. et al. Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice. Psychopharmacology 232, 1471–1482 (2015). https://doi.org/10.1007/s00213-014-3784-y

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Keywords

  • μ-Opioid receptor (MOP)
  • Knockout (KO) mice
  • Social isolation
  • Stress
  • Sex-dependent manner
  • Abuse
  • Alcoholism