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Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors

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Abstract

The number of cannabis users is increasing in the world. However, the mechanisms involved in the psychiatric effects and addiction formation remain unclear. Medical treatments against cannabis addiction have not yet been established. Δ9-Tetrahydrocannabinol (THC), the main active substance in cannabis, binds and affects cannabinoid type 1 receptors (CB1R) in the brain. The mice were intraperitoneally (i.p.) administered arachidonylcyclopropylamide (ACPA), a CB1R-selective agonist, and then two behavioral experiments on anxiety and addiction were performed. Administration of ACPA caused anxiolytic-like behavior in the elevated plus maze test. In addition, ACPA increased place preference in a conditioned place preference (CPP) test. The basolateral amygdala (BLA), which is the focus of this study, is involved in anxiety-like behavior and reward and is reported to express high levels of CB1R. We aimed to reveal the role of CB1R in BLA for ACPA-induced behavior. AM251, a CB1R selective antagonist, was administered intra-BLA before i.p. administration of ACPA. Intra-BLA administration of AM251 inhibited ACPA-induced anxiolytic-like behavior and place preference. These results suggest that CB1R in the BLA contributes to behavior disorders caused by the acute or chronic use of cannabis.

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Data Availability

The data presented in this manuscript are available upon request from the corresponding authors on reasonable request.

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Acknowledgements

We thank Prof Satoshi Morimoto, Kyusyu University, for supplying THC for pre-study.

Funding

This work was supported by the Grant-in-aid for Scientific Research (KAKENHI) (B) [JSPS KAKENHI JP21H02632], JP22J11998, JP16H06276 (AdAMS) from the Japan Society for the Promotion of Science, Kobayashi Foundation, and SRF Grant for Biomedical Research and Foundation. The funders had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.

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  1. Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Tomohiro Tokutake, Takashi Asano, Hajime Miyanishi, Shigetoshi Nakaya, Naotaka Izuo & Atsumi Nitta

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  1. Tomohiro Tokutake
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Contributions

All the authors contributed to the conception and design of the study. Material preparation, data collection and analysis were performed by TT, TA, and SN. The first manuscript was written by TT and HM. AN revised the manuscript to the final version. All the authors commented on the previous versions of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Atsumi Nitta.

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

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Animal experimental protocols were by the animal Care and Use Committee of the University of Toyama (Approval Number: A2020PHA14) and conducted in accordance with the Institutional Animal Experiment Handling Rules of the University of Toyama. The number of animals used was carefully estimated and kept to the minimum necessary for meaningful interpretation of the data.

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Tokutake, T., Asano, T., Miyanishi, H. et al. Cannabinoid Type 1 Receptors in the Basolateral Amygdala Regulate ACPA-Induced Place Preference and Anxiolytic-Like Behaviors. Neurochem Res 47, 2899–2908 (2022). https://doi.org/10.1007/s11064-022-03708-8

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