The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats

Abstract

Rationale

Preclinical studies indicate that gonadal hormones are important determinants of drug self-administration. To date, little is known about the influence of sex and estrous cycle on drug self-administration in ecologically relevant social contexts.

Objective

The objective of this study was to examine the role of sex and estrous cycle in a rat model during cocaine and heroin self-administration with male-female and female-female social dyads.

Methods

Male and female virgin rats were trained to self-administer cocaine and heroin in operant conditioning chambers that permitted two rats to self-administer concurrently, but prevented physical contact. Experiment 1 examined cocaine self-administration on a progressive ratio schedule in male-female dyads. Experiments 2 and 3 examined heroin self-administration on a fixed ratio schedule in male-female dyads at constant and varying doses, respectively. Experiment 4 examined heroin self-administration in female-female dyads on a fixed ratio schedule.

Results

Cocaine-maintained breakpoints increased by ∼17 % in females during estrus, but remained consistent in males. Heroin self-administration decreased by ∼70 % during proestrus in females whether they were isolated, housed with males, or housed with females. Heroin self-administration was lower in males than females under some conditions and was not consistently associated with the responding of females.

Conclusions

Cocaine and heroin self-administration is influenced by the estrous cycle in females when in the presence of a male partner. As a novel finding, these data illustrate that heroin self-administration is reduced in females during proestrus regardless of the social context tested. Finally, these data suggest that drug self-administration in males is only minimally influenced by the hormonal status of a female partner.

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Acknowledgments

The authors thank Sarah Bills for expert technical assistance and the National Institute on Drug Abuse for supplying the study drugs.

This study was funded by NIH Grants DA027485 and DA031725.

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Correspondence to Mark A. Smith.

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Lacy, R.T., Strickland, J.C., Feinstein, M.A. et al. The effects of sex, estrous cycle, and social contact on cocaine and heroin self-administration in rats. Psychopharmacology 233, 3201–3210 (2016). https://doi.org/10.1007/s00213-016-4368-9

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Keywords

  • Cocaine
  • Estrous
  • Heroin
  • Self-administration
  • Sex
  • Social