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Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion

Abstract

Rationale

Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear.

Objectives

The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion.

Methods

Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding.

Results

Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine.

Conclusions

Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.

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Acknowledgments

We also thank Dr. Jeffrey Stevens, Dr. Ming Li, and Dr. Samuel Allgood for providing insightful comments on an earlier version of this manuscript. Finally, we also thank Cindy Pudiak, Olivia Loh, Tiffany Schultz, Hannah Sellyer, and Aly Lange for help with conducting daily experimental sessions.

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Correspondence to Scott T. Barrett.

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Funding

The authors and this research were in part supported by a grant from the National Institute on Drug Abuse (DA034389).

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The authors declare that they have no conflict of interest.

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Barrett, S.T., Geary, T.N., Steiner, A.N. et al. Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion. Psychopharmacology 234, 187–198 (2017). https://doi.org/10.1007/s00213-016-4448-x

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  • DOI: https://doi.org/10.1007/s00213-016-4448-x

Keywords

  • Nicotine
  • Bupropion
  • Sex differences
  • Reward enhancement
  • Behavioral economics
  • Reinforcer demand
  • Dopamine
  • Rats