Effects of Serial Polydrug Use on the Rewarding and Aversive Effects of the Novel Synthetic Cathinone Eutylone

Abstract

Background: As individual synthetic cathinones become scheduled and regulated by the Drug Enforcement Administration (DEA), new ones regularly are produced and distributed. One such compound is eutylone, a novel third-generation synthetic cathinone whose affective properties (and abuse potential) are largely unknown. The following experiments begin to characterize these effects and how they may be impacted by drug history (a factor affecting reward/aversion for other drugs of abuse). Methods: Eutylone was assessed for its ability to induce conditioned taste avoidance (CTA; aversive effect) and conditioned place preference (CPP; rewarding effect) and their relationship (Experiment 1). Following this, the effects of exposure to cocaine or 3,4-methylenedioxymethamphetamine [MDMA] on eutylone’s affective properties were investigated (Experiment 2). Results: Eutylone produced dose-dependent CTA and CPP (Experiment 1), and these endpoints were unrelated. Pre-exposure to cocaine and MDMA differentially impacted taste avoidance induced by eutylone (MDMA > cocaine) and did not impact eutylone-induced place preference. Conclusions: These data indicate that eutylone, like other synthetic cathinones, has co-occurring, independent rewarding and aversive effects that may contribute to its abuse potential and that these effects are differentially impacted by drug history. Although these studies begin the characterization of eutylone, future studies should examine the impact of other factors on eutylone’s affective properties and its eventual reinforcing effects (i.e., intravenous self-administration [IVSA]) to predict its use and abuse liability.

Synthetic Cathinones: Epidemiology, Toxicity, Potential for Abuse, and Current Public Health Perspective

“…Eutylone, one of the third-generation SCs, produced dose-dependent CPP in male mice [114] and female rats [115]. Interestingly, pre-exposure to cocaine and MDMA did not have any effects on the development of eutylone-induced CPP [114].…”

“…For instance, both 2-cyclohexyl-2-(methylamino)-1phenylethanone (MACHP, Figure 1) and 2-(methylamino)-1-phenyloctan-1-one (MAOP, Figure 1) produced CPP, but only MACHP was found to be self-administered [113]. Eutylone, one of the third-generation SCs, produced dose-dependent CPP in male mice [114] and female rats [115]. Interestingly, pre-exposure to cocaine and MDMA did not have any effects on the development of eutylone-induced CPP [114].…”

Structure–Activity Relationship of Synthetic Cathinones: An Updated Review

“…81,84 It is important to highlight that the final subjective experience will be conditioned by multiple factors including the drug (dose, purity, route, substance, drug combination), the user (age, sex, race, genetic predispositions, individual's mental and physical condition, sleep, nutrition, history of drug use, interactions, purpose of use, mood) and the setting (environment, company, peer pressure). 85,86 The primary effects sought by users include euphoria, increased energy and alertness, elevated mood and sense of well-being, increased motivation and empathy, productivity and work capacity, self-confidence, sociability, talkativeness, hallucinations, insomnia, reduced appetite, increased libido, and sexual drive. 83,87,88 The side effects can be divided into somatic effects, which include tachycardia, hypertension, nausea, vomiting, mydriasis, seizures, hyperthermia, bruxism, nasal irritation, dry mouth, and difficulty urinating; and psychological effects, which include anxiety unpleasant 'comedown, hallucinations, confusion, anorexia, psychosis, compulsive use and dependence symptoms.…”