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Levodopa reduces consumption of multiple classes of addictive substances in rats

Farero, R. D.; Holtz, N. A.; Lee, S. J.; Kruse, L. C.; Clark, J. J.; Phillips, P. E. M.

2023-12-15 animal behavior and cognition
10.1101/2023.12.14.570833 bioRxiv
Show abstract

Dopamine transmission is implicated in aberrant behaviors associated with substance use disorders. Previous research revealed a causal link between excessive drug consumption and the loss of dopamine signaling to stimuli associated with psychostimulant use. The emerging change in dopamine signaling is specific to stimuli associated with the substance rather than the pharmacological properties of the drug itself. Because the change in dopamine signaling was specific to the associated stimuli and not the pharmacological properties of the substance, we examined if treatment with the dopamine precursor, L-DOPA, alters alcohol and opioid self-administration. Therefore, we trained rats to orally self-administer ethanol or the synthetic opioid fentanyl and found that treating animals with L-DOPA significantly reduced consumption of both alcohol and fentanyl. These data suggest dopamine signaling has a vital role in mediating the amount of drug animals will voluntarily take, across multiple classes of drugs. Importantly, these data are preclinical demonstrations of L-DOPA being utilized as a harm reducing treatment in substance use disorders.

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