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Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner

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Abstract

The effects of prenatal opioid exposure in adult animals has been widely studied, but little is known about the effects of prenatal opioid on adolescents. Most of the risk behaviors associated with drug abuse are initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiate drug use and susceptible to drug-induced brain changes. In this study, pregnant rats were subcutaneously injected with an increasing dose of morphine (5 mg/kg, 7 mg/kg, 10 mg/kg) for 9 days since the gestation day 11. The effects of prenatal morphine (PNM) on learning and memory, anxiety- and depressive- like behavior, morphine induced conditioned place preference (CPP) as well as locomotor sensitization were tested in both adolescent and adult rats. The results showed that: (1) PNM decreased anxiety-like behavior in both adolescent and adult female rats, but not males; (2) PNM decreased depressive-like behavior in adolescent but increased depressive -like behavior in adult females; (3) PNM increased low dose morphine induced locomotor sensitization in females; (4) PNM decreased tyrosine hydroxylase (TH) expression in the prefrontal cortex but decreased dopamine D1 receptor expression in the nucleus-accumbens (NAc) in female rats. These results suggested that PNM altered the emotional and addictive behavior mainly in female rats, with female rats being less anxiety and depressive during adolescence, but more depressive in adult, and more sensitive to low dose morphine induced locomotor activity sensitization, which might be mediated in part by the differential expression of the TH, dopamine D1 receptors in the female brain.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81760251, 32060196) and the Yunnan high-level talent special support plan (YNWR-QNBJ-2018-026).

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Authors and Affiliations

  1. Department of Basic Medicine, Medical School, Kunming University of Science and Technology, #727 South Jingming Road, 650550, Kunming, Yunnan, China

    Yanmei Chen, Miaomiao Du, Na Kang, Xin Guan, Bixue Liang, Zhuangfei Chen &  Jichuan Zhang

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  1. Yanmei Chen
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  2. Miaomiao Du
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  3. Na Kang
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  4. Xin Guan
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  6. Zhuangfei Chen
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  7. Jichuan Zhang
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Contributions

Yanmei Chen designed the project, performed partial behavioral experiments, supervised the experiments, analyzed the data and wrote the manuscript; Miaomiao Du, Na Kang, Xin Guan and Bixue Liang performed the behavioral experiments;Zhuangfei Chen performed partial data analysis and revised the manuscript; Jichuan Zhang designed the project, supervised the experiments, performed partial data analysis, and revised the manuscript.

Corresponding authors

Correspondence to Yanmei Chen or Jichuan Zhang.

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Conflict of Interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical Approval

All experiments were conducted in accordance with the guidelines for National Care and Use of Animals approved by the National Animal Research Authority. Protocols were approved by the Medical Animal Care & Welfare Committee of Kunming University of Science and Technology (No. 2017JC002).

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Chen, Y., Du, M., Kang, N. et al. Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner. Neurochem Res 47, 2317–2332 (2022). https://doi.org/10.1007/s11064-022-03619-8

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  • DOI: https://doi.org/10.1007/s11064-022-03619-8

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