2. Academic Validation
  3. The psychomotor, reinforcing, and discriminative stimulus effects of synthetic cathinone mexedrone in male mice and rats

The psychomotor, reinforcing, and discriminative stimulus effects of synthetic cathinone mexedrone in male mice and rats

  • Eur J Pharmacol. 2024 Feb 29:176466. doi: 10.1016/j.ejphar.2024.176466.
Kyung Oh Jeon 1,  Oc-Hee Kim 2,  Soo Yeon Seo 3,  Jaesuk Yun 4,  Choon-Gon Jang 5,  Ri-Na Lim 2,  Tae Wan Kim 2,  Chae Ha Yang 6,  Seong Shoon Yoon 7,  Eun Young Jang 8
Affiliations

Affiliations

  • 1 Department of Advanced Toxicology Research, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea; Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
  • 2 Department of Advanced Toxicology Research, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea.
  • 3 Korean Medicine (KM) Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea.
  • 4 College of Pharmacy, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28160, Republic of Korea.
  • 5 Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 6 Department of Physiology, College of Korean Medicine, Daegu Haany University, 136 Sincheondong-ro, Suseong-gu, Daegu, 42158, Republic of Korea.
  • 7 Department of Physiology, College of Korean Medicine, Daegu Haany University, 136 Sincheondong-ro, Suseong-gu, Daegu, 42158, Republic of Korea. Electronic address: ssyoon@dhu.ac.kr.
  • 8 Department of Advanced Toxicology Research, Korea Institute of Toxicology, Daejeon, 34114, Republic of Korea. Electronic address: eunyoung.jang@kitox.re.kr.
PMID: 38431243 DOI: 10.1016/j.ejphar.2024.176466
Abstract

The chronic use of the novel synthetic cathinone mexedrone, like Other psychoactive drugs, can be considered addictive, with a high potential for abuse and the ability to cause psychological dependence in certain users. However, little is known about the neurobehavioral effects of mexedrone in association with its potential for abuse. We investigated the abuse potential for mexedrone abuse through multiple behavioral tests. In addition, Serotonin Transporter (SERT) levels were measured in the synaptosome of the dorsal striatum, and serotonin (5-HT) levels were measured in the dorsal striatum of acute mexedreone (50 mg/kg)-treated mice. To clarify the neuropharmacological mechanisms underlying the locomotor response of mexedrone, the 5-HT2A receptor antagonist M100907 (0.5 or 1.0 mg/kg) was administered prior to the acute injection of mexedrone in the locomotor activity experiment in mice. Mexedrone (10-50 mg/kg) produced a significant place preference in mice and mexedrone (0.1-0.5 mg/kg/infusion) maintained self-administration behavior in rats in a dose-dependent manner. In the drug discrimination experiment, mexedrone (5.6-32 mg/kg) fully substituted for the discriminative stimulus effects of cocaine in rats. Mexedrone increased locomotor activity, and these effects were reversed by pretreatment with M100907. Acute mexedrone significantly increased c-Fos expression in the dorsal striatum and decreased SERT levels in the synaptosome of the dorsal striatum of mice, resulting in elevation of 5-HT levels. Taken together, our results provide the possibility that mexedrone has the abuse potential, which might be mediated, at least in part, by the activation of the serotonergic system in the dorsal striatum.

Keywords

Abuse potential; Dorsal striatum; Mexedrone; Reinforcing effects; Serotonin; Synthetic cathinone.

Figures
Products