Methylone produces antidepressant-relevant actions and prosocial effects

Zhenlong Li, Hsien Yu Peng, Chau Shoun Lee, Tzer Bin Lin, Ming Chun Hsieh, Cheng Yuan Lai, Han Fang Wu, Lih Chyang Chen, Mei Ci Chen, Dylan Chou

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Methylone (3,4-methylenedioxy-N-methylcathinone) is a rapid-acting entactogen that has been shown to have significant benefits in patients with post-traumatic stress disorder and major depressive disorder and is well tolerated in phase 1 clinical trials. A recent preclinical study reported that methylone produced robust antidepressant-like actions in naïve rats. However, its antidepressant effects on various stress-related psychopathologies and other neuropsychological actions remain unclear. In the present study, we examined the antidepressant-relevant effects of methylone in learned helplessness (LH) and social defeat stress C57BL/6J male mouse models and further explored its sociability-relevant neuropsychological actions. Our results indicate that methylone produces antidepressant-relevant effects on the helpless phenotype, LH-evoked depressive-like behaviors, and psychosocial stress-induced social avoidance, and induced depressive-like behaviors. In addition, methylone was found to enhance social preference and increase various social behaviors, including social contact, sniffing, allogrooming, and following. Moreover, methylone appeared to elevate empathy-like phenotypes and was also found to increase helping-like behavior. Overall, the present results suggest that methylone plays an antidepressant-like role in various stress-relevant psychopathologies and could be an ideal antidepressant candidate. In addition, novel findings on the elevated tendencies of social preference and empathy-like and helping-like phenotypes reveal that methylone may have potential application in patients with social deficits.

Original languageEnglish
Article number109787
Publication statusPublished - Jan 1 2024


  • Antidepressant
  • Depressive-like behavior
  • Empathy-like behavior
  • Helping-like behavior
  • Methylone
  • Sociability

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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