Relative reinforcing effects of dibutylone, ethylone, and N-ethylpentylone self-administration and behavioral economics analysis in rats.
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 mgkg) 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 mgkg), dibutylone (0.1 mg·kg 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.