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Prenatal exposure to morphine impairs attention and impulsivity in adult rats

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Abstract

Rationale

An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life.

Methods

On embryonic days 11–18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1 ml/kg), naloxone (1 mg/kg), and acute morphine (1, 3, 5 mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance.

As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5 mg/kg morphine for 5 days and then naloxone in the last day of the experiment (day 6).

Results

Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone.

Conclusion

The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood.

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Acknowledgements

We are immensely grateful to Professor Jeff Dalley (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

    Elham Alaee, Parisa Moazen, Saeed Semnanian & Hossein Azizi

  2. Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam, The Netherlands

    Tommy Pattij

  3. Institute for Brain Sciences and Cognition, Tarbiat Modares University, Tehran, Iran

    Hossein Azizi

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  1. Elham Alaee
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Alaee, E., Moazen, P., Pattij, T. et al. Prenatal exposure to morphine impairs attention and impulsivity in adult rats. Psychopharmacology 238, 2729–2741 (2021). https://doi.org/10.1007/s00213-021-05888-7

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