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Involvement of Hippocampal D1-Like Dopamine Receptors in the Inhibitory Effect of Cannabidiol on Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference

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Abstract

Cannabidiol (CBD) is a non-psychotomimetic compound with strong potential to decrease the psychostimulant’s rewarding effect with unclear receptors. Furthermore, as a part of the reward circuit, the hippocampus plays a crucial role in regulating the reward properties of drugs as determined by conditioned place preference (CPP). In the current research, CPP was used to evaluate the role of intra-CA1 microinjection of D1-like dopamine receptor antagonists in CBD's inhibitory effect on the acquisition and expression phases of methamphetamine (METH). Animals were treated by METH (1 mg/kg; sc) in a five-day schedule to induce CPP. To find out the impact of D1-like dopamine receptor antagonist, SCH23390, in the CA1 on the inhibitory influence of CBD on the acquisition of METH, the rats received intra-CA1 administration of SCH23390 (0.25, 1, and 4 µg/0.5 µl) following ICV treatment of CBD (10 µg/5 µl) over conditioning phase of METH. Furthermore, animals were given SCH23390 in the CA1 ensuing ICV microinjection of CBD (50 µg/5 µl) in the expression phase of METH to rule out the influence of SCH23390 on the suppressive effect of CBD on the expression of METH CPP. Intra-CA1 microinjection of SCH23390 abolished CBD's suppressive impact on both METH-induced CPP phases without any side effect on the locomotion. The current research disclosed that CBD inhibited the rewarding characteristic of METH via D1-like dopamine receptors in the CA1 region of the hippocampus.

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Acknowledgements

This project was supported by the Vice-Chancellor for Research & Technology of Shahid Beheshti University of Medical Sciences (Grant No. 00-26809-1400-01-25). Also the authors would like to thank the Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran for conducting this study.

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Authors and Affiliations

  1. Pharmacology and Toxicology Department, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Kiana Nouri, Mahsa Anooshe & Zahra Mousavi

  2. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Saeideh Karimi-Haghighi

  3. Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, 19615-1178, Tehran, Iran

    Abbas Haghparast

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  1. Kiana Nouri
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  2. Mahsa Anooshe
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  4. Zahra Mousavi
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Contributions

AH was responsible for the study concept and design. KN and MA contributed to the acquisition of behavioral data. AH, SK-H and ZM assisted with data analysis and interpretation of findings. KN and SK-H drafted the manuscript. AH provided critical revision of the manuscript for important intellectual content. All authors critically reviewed content and approved the final version for publication.

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Correspondence to Abbas Haghparast.

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Nouri, K., Anooshe, M., Karimi-Haghighi, S. et al. Involvement of Hippocampal D1-Like Dopamine Receptors in the Inhibitory Effect of Cannabidiol on Acquisition and Expression of Methamphetamine-Induced Conditioned Place Preference. Neurochem Res 46, 2008–2018 (2021). https://doi.org/10.1007/s11064-021-03350-w

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  • DOI: https://doi.org/10.1007/s11064-021-03350-w

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