Abstract
Rationale
Methamnetamine (MNA; PAL-1046) is a new psychoactive substance that acts as a full biogenic amine transporter (BAT) substrate. BAT substrates promote neurotransmitter release from the nerve terminal and can be abused as stimulants. However, scientific information on the abuse potential of methamnetamine is lacking.
Objective
We evaluated the abuse liability of methamnetamine.
Methods
The effective dose range of methamnetamine was determined using a climbing behavior test. The rewarding effect and reinforcing effect of the test compound were evaluated in mice by conditioned place preference (CPP) testing and self-administration (SA) testing at the selected doses. Dopamine level changes were analyzed using synaptosomes and in vivo microdialysis to investigate the effects of methamnetamine on the central nervous system. Drug discrimination experiments were used to examine the potential similarity of the interoceptive effects of methamnetamine and cocaine.
Results
A significant response was observed in the climbing behavior test with 10 and 40 mg/kg intraperitoneally administered methamnetamine. In the CPP test, mice intraperitoneally administered methamnetamine (10 and 20 mg/kg) showed a significant preference for the drug-paired compartment. In the SA test, mice that intravenously received 1 mg/kg/infusion showed significant active-lever responses. Dopamine was significantly increased in synaptosomes and in in vivo microdialysis tests. Furthermore, methamnetamine showed cross-generalization with cocaine in a dose-dependent manner.
Conclusions
Methamnetamine exhibits interceptive stimulus properties similar to those of cocaine and induces rewarding and reinforcing effects, suggesting its dependence liability potential.
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Acknowledgements
We would like to thank Editage (www.editage.co.kr) for English language editing.
Funding
This research was supported by a grant (MFDS-7036-306/19181MFDS401/19181MFDS402) from the National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Republic of Korea in 2020.
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Youn, DH., Kim, J.M., Hong, Yk. et al. Assessment of the abuse potential of methamnetamine in rodents: a behavioral pharmacology study. Psychopharmacology 238, 2155–2165 (2021). https://doi.org/10.1007/s00213-021-05840-9
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DOI: https://doi.org/10.1007/s00213-021-05840-9