Relative reinforcing effects of dibutylone, ethylone, and N-ethylpentylone: self-administration and behavioral economics analysis in rats.
Miaojun Lai, Dan Fu, Zeming Xu, Han Du, Huifen Liu, Youmei Wang, Peng Xu, Wenhua Zhou
Psychopharmacology September 2022 DOI: 10.1007/s00213-022-06173-x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | Methamphetamine Dibutylone Ethylone N-ethylpentylone |
| Dose | METH 0.05 mg/kg; dibutylone 0.1 mg·kg-1·infusion-1; ethylone 0.4 mg·kg-1·infusion-1; N-ethylpentylone 0.1 mg·kg-1·infusion-1 |
| Keywords | Dibutylone Ethylone Methamphetamine N-ethylpentylone Reinforcing effect Self-administration Synthetic cathinone |
| Key findings | Dibutylone, ethylone, and N-ethylpentylone functioned as reinforcers in rats, with reinforcing potency ranked methamphetamine > N-ethylpentylone ≈ dibutylone > ethylone. Essential value ranked methamphetamine (7.93) ≈ dibutylone (7.81) > N-ethylpentylone (5.21) ≈ ethylone (4.19). The authors suggest these compounds have addictive potential and that α-alkyl and N-alkyl side chain modifications may affect reinforcing efficacy. |
Abstract
Following the emergence of methylone as one of the most popular synthetic cathinones, this group of novel psychoactive substance with names ending in "-lone," such as dibutylone, ethylone, and N-ethylpentylone, appeared on the recreational drug market. The pharmacological mechanisms of dibutylone, ethylone, and N-ethylpentylone are well understood; however, to date, the reinforcing effects of dibutylone, ethylone, and N-ethylpentylone are still unclear. This study aimed to examine the self-administration of dibutylone, ethylone, and N-ethylpentylone relative to methamphetamine (METH) and to quantify their relative reinforcing effectiveness using behavioral economic analysis. Male Sprague-Dawley rats were trained to self-administer METH (0.05 mg/kg) under a fixed-ratio 1 (FR1) schedule. Following the training, dose substitution was used to generate full dose-response curves for METH and the three synthetic cathinones. According to the first doses on the descending limb of the dose-response curves, rats were trained to self-administer METH (0.05 mg/kg), dibutylone (0.1 mg·kg-1·infusion-1), ethylone (0.4 mg·kg-1·infusion-1), or N-ethylpentylone (0.1 mg·kg-1·infusion-1) under an FR1 schedule, and a behavioral economic evaluation of their reinforcing effectiveness was then performed. Dibutylone, ethylone, and N-ethylpentylone functioned as reinforcers, and the inverted U-shaped dose-response curves were obtained. The rank order of reinforcing potency in this procedure was METH > N-ethylpentylone ≈ dibutylone > ethylone. In the economic analysis, the comparisons of the essential value (EV) transformed from demand elasticity (α) indicated that the rank order of efficacy as reinforcers was METH (EV = 7.93) ≈ dibutylone (EV = 7.81) > N-ethylpentylone (EV = 5.21) ≈ ethylone (EV = 4.19). These findings demonstrated that dibutylone, ethylone, and N-ethylpentylone function as reinforcers and have addictive potential, suggesting that the modification of α-alkyl and N-alkyl side chains may affect their reinforcing efficacy.