Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring

Toussaint, A. B.; Ellis, A. S.; Bongiovanni, A. R.; Peterson, D. R.; Bavley, C. C.; Karbalaei, R.; Mayberry, H. L.; Bhakta, S.; Dressler, C. C.; Imperio, C. G.; Maurer, J. J.; Schmidt, H. D.; Chen, C.; Bland, K.; Liu-Chen, L.-Y.; Wimmer, M. E.

doi:10.1101/2023.01.03.522600

bioRxiv · 10.1101/2023.01.03.522600

Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring

Toussaint, A. B.·Ellis, A. S.·Bongiovanni, A. R.·Peterson, D. R.·Bavley, C. C.·Karbalaei, R.·Mayberry, H. L.·Bhakta, S.·Dressler, C. C.·Imperio, C. G.·Maurer, J. J.·Schmidt, H. D.·Chen, C.·Bland, K.·Liu-Chen, L.-Y.·Wimmer, M. E.

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Abstract

BackgroundA growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation. MethodsAdult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naive dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naive F1 offspring. ResultsMale, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens. ConclusionsPaternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.

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Toussaint, A. B., Ellis, A. S., Bongiovanni, A. R., Peterson, D. R., Bavley, C. C., Karbalaei, R., Mayberry, H. L., Bhakta, S., Dressler, C. C., Imperio, C. G., Maurer, J. J., Schmidt, H. D., Chen, C., Bland, K., Liu-Chen, L.-Y., Wimmer, M. E.. 2023-01-04. Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring. https://doi.org/10.1101/2023.01.03.522600

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