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Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function

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Abstract

Rationale

The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring.

Objectives

In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure.

Methods

We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generations) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine.

Results

Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion and upregulated kappa opioid receptor and dopamine D2 receptor (D2R) gene expression within the nucleus accumbens.

Conclusions

These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior.

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Acknowledgments

This work was supported by NIH R01DA25674 (EMB).

Conflict of interest

All authors declare that, except for income received from our primary employer, no financial support or compensation has been received from any individual or corporate entity for this research or related professional service. There are no personal financial holdings that could be perceived as constituting a potential conflict of interest. The authors have full control of all primary data and that they agree to allow the journal to review their data if requested.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA, 01536, USA

    John J. Byrnes, Nicole L. Johnson, Lindsay M. Carini & Elizabeth M. Byrnes

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  1. John J. Byrnes
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  2. Nicole L. Johnson
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  3. Lindsay M. Carini
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  4. Elizabeth M. Byrnes
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Correspondence to John J. Byrnes.

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Byrnes, J.J., Johnson, N.L., Carini, L.M. et al. Multigenerational effects of adolescent morphine exposure on dopamine D2 receptor function. Psychopharmacology 227, 263–272 (2013). https://doi.org/10.1007/s00213-012-2960-1

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  • DOI: https://doi.org/10.1007/s00213-012-2960-1

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