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Dopamine D5 receptor modulates male and female sexual behavior in mice

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Abstract

Rationale

Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses.

Objective

This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates.

Methods

Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone (P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference.

Results

Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context.

Conclusions

In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine’s action on sexual behavior in both sexes, perhaps via a reward pathway.

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Acknowledgements

The authors would like to thank Aileen Wills and Savera Shetty for technical assistance. We thank Dr. Melissa Burns-Cusato for insightful comments on the final draft of this paper. This work was supported by NIH grants R01 MH57759 and K02 MH01349 (EFR). AEK was supported by NIH training grant HD072323.

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Authors and Affiliations

  1. Neuroscience Graduate Program, University of Virginia Medical School, Charlottesville, VA, 22908, USA

    A. E. Kudwa & E. F. Rissman

  2. Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA, 22908, USA

    E. Dominguez-Salazar & E. F. Rissman

  3. Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, 20892, USA

    D. M. Cabrera & D. R. Sibley

Authors
  1. A. E. Kudwa
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  2. E. Dominguez-Salazar
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  3. D. M. Cabrera
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  4. D. R. Sibley
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  5. E. F. Rissman
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Corresponding author

Correspondence to E. F. Rissman.

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A.E. Kudwa and E. Dominguez-Salazar are co-authors.

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Kudwa, A.E., Dominguez-Salazar, E., Cabrera, D.M. et al. Dopamine D5 receptor modulates male and female sexual behavior in mice. Psychopharmacology 180, 206–214 (2005). https://doi.org/10.1007/s00213-005-2150-5

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  • DOI: https://doi.org/10.1007/s00213-005-2150-5

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