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Publication : The ion channel TRPA1 is a modulator of the cocaine reward circuit in the nucleus accumbens.

First Author  Kim YJ Year  2024
Journal  Mol Psychiatry PubMed ID  38822069
Mgi Jnum  J:353389 Mgi Id  MGI:7711076
Doi  10.1038/s41380-024-02623-4 Citation  Kim YJ, et al. (2024) The ion channel TRPA1 is a modulator of the cocaine reward circuit in the nucleus accumbens. Mol Psychiatry
abstractText  Drug addiction therapies commonly fail because continued drug use promotes the release of excessive and pleasurable dopamine levels. Because the connection between pleasure and drug use becomes hard-wired in the nucleus accumbens (NAc), which interfaces motivation, effective therapies need to modulate this mesolimbic reward system. Here, we report that mice with knockdown of the cation channel TRPA1 (transient receptor potential ankyrin 1) were resistant to the drug-seeking behavior and reward effects of cocaine compared to their wildtype litter mates. In our study, we demonstrate that TRPA1 inhibition in the NAc reduces cocaine activity and dopamine release, and conversely, that TRPA1 is critical for cocaine-induced synaptic strength in dopamine receptor 1-expressing medium spiny neurons. Taken together, our data support that cocaine-induced reward-related behavior and synaptic release of dopamine in the NAc are controlled by TRPA1 and suggest that TRPA1 has therapeutic potential as a target for drug misuse therapies.
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