New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents

Fühner-Wieland's Sammlung von Vergiftungsfällen - Tập 95 - Trang 1413-1429 - 2021
Young-Jung Kim1, Shi-Xun Ma1, Kwang-Hyun Hur1, Youyoung Lee1, Yong-Hyun Ko1, Bo-Ram Lee1, Seon-Kyung Kim1, Su-Jeong Sung1, Kyeong-Man Kim2, Hyoung-Chun Kim3, Seok-Yong Lee1, Choon-Gon Jang1
1Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea
2Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea
3Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea

Tóm tắt

2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of 4-chloro-2,5-dimethoxyphenethylamine (2C-C) and 2,5-dimethoxy-4-propylphenethylamine (2C-P). We found that 2C-C and 2C-P produced conditioned place preference in a dose-dependent manner in mice, and increased self-administration in rats, suggesting that 2C-C and 2C-P have abuse potential. To investigate the neurotoxicity of 2C-C and 2C-P, we examined motor performance and memory impairment after high doses of 2C-C and 2C-P. High doses of 2C-C and 2C-P decreased locomotor activity, rota-rod performance, and lower Y-maze test, novel objective recognition test, and passive avoidance test scores. We also observed that 2C-C and 2C-P affected expression levels of the D1 dopamine receptor, D2 dopamine receptor, dopamine transporter, and phospho-dopamine transporter in the nucleus accumbens and the medial prefrontal cortex, and increased c-Fos immuno-positive cells in the nucleus accumbens. Moreover, high doses of 2C-C and 2C-P induced microglial activation, which is involved in the inflammatory reaction in the striatum. These results suggest that 2C-C and 2C-P have abuse potential by affecting dopaminergic signaling and induce neurotoxicity via initiating neuroinflammation at high doses.

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