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Mol. Psychiatr., May 31 2024, | https://doi.org/10.1038/s41380-024-02623-4 The ion channel TRPA1 is a modulator of the cocaine reward circuit in the nucleus accumbens

Young-Jung Kim^1,5, Su Jeong Choi^2,5, Sa-Ik Hong^1,5, Jung-Cheol Park^2,5, Youyoung Lee¹, Shi-Xun Ma¹, Kwang-Hyun Hur¹, Young Lee², Kyeong-Man Kim³, Hyung Kyu Kim⁴, Hee Young Kim⁴, Seok-Yong Lee¹, Se-Young Choi²and Choon-Gon Jang¹

¹Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

²Department of Physiology, Dental Research Institute, Seoul National University School of Dentistry, Seoul 03080, Republic of Korea.

³Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.

⁴Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

⁵These authors contributed equally: Young-Jung Kim, Su Jeong Choi, Sa-Ik Hong, Jung-Cheol Park.

Corresponding authors

Correspondence to Se-Young Choi or Choon-Gon Jang.

Abstract

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-06-04)
연구진국내 연구진
분야 의약학 > 약학

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