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Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny

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Abstract

Rationale

Identifying the long-term neurocognitive implications of opioid addiction may further our understanding of the compulsive nature of this brain disorder. The aim of this study was to examine the effects of paternal adolescent opiate exposure on cognitive performance (visual attention, impulsivity, and compulsivity) in the next generation.

Methods

Male Wistar rats received escalating doses of morphine (2.5–25 mg/kg, s.c.) or saline for 10 days during adolescence (P30–39). In adulthood (P70–80), these rats were allowed to mate with drug-naive females. Male offspring from morphine- and saline-exposed sires, once in adulthood, were trained and tested in the 5-choice serial reaction time test (5-CSRTT) to evaluate their cognitive abilities under baseline, drug-free conditions as well as following acute (1, 3, 5 mg/kg morphine) and subchronic morphine (5 mg/kg morphine for 5 days) treatment. Behavioral effects of the opioid receptor antagonist naloxone were also assessed.

Results

Morphine-sired offspring exhibited delayed learning when the shortest stimulus duration (1 s) was introduced, i.e., when cognitive load was highest. These subjects also exhibited a reduced ability to exert inhibitory control, as reflected by increased premature and perseverative responding under drug-free baseline conditions in comparison to saline-sired rats. These impairments could not be reversed by administration of naloxone. Moreover, impulsive behavior was further enhanced in morphine-sired rats following acute and subchronic morphine treatment.

Conclusion

Paternal opiate exposure during adolescence was found to primarily impair inhibitory control in male progeny. These results further our understanding of the long-term costs and risk of opioid abuse, extending across generations.

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Acknowledgements

We are immensely grateful to Professor Trevor Robbins (Department of Psychiatry, University of Cambridge) for helpful comments on the manuscript. In addition, we would like to thank the financial support of the Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Maryam Azadi, Parisa Moazen, Saeed Semnanian & Hossein Azizi

  2. Center for Social and Affective Neuroscience, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden

    Joost Wiskerke

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  1. Maryam Azadi
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  2. Parisa Moazen
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Azadi, M., Moazen, P., Wiskerke, J. et al. Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny. Psychopharmacology 238, 3435–3446 (2021). https://doi.org/10.1007/s00213-021-05962-0

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