Pre-exposure to eutylone attenuates its own aversive effects but has no impact on cocaine or MDMA: A possible role of eutylone's hybrid pharmacology.
Negar G Ardabili, Shira Tan, Anthony L Riley
Pharmacology, Biochemistry, and Behavior July 1, 2025 DOI: 10.1016/j.pbb.2025.174013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Interventions | Eutylone Cocaine MDMA |
| Dose | 20 mg/kg |
| Topics | MDMA |
| Keywords | Cocaine Conditioned taste avoidance Drug pre-exposure Eutylone Reuptake inhibition Substrate releaser Neuropharmacology Drug tolerance Stimulant drugs Drug interactions Behavioral pharmacology |
| Citations | 1 |
| Key findings | Pre-exposure to eutylone attenuated taste avoidance induced by eutylone itself but did not affect cocaine- or MDMA-induced taste avoidance in male rats. |
Abstract
Previous research has reported that pre-exposure to a variety of drugs of abuse can impact (reduce) the aversive effects of themselves and other abused compounds, often as a function of their shared pharmacological activity. In this context, the present series of studies investigated the effects of history with the synthetic cathinone eutylone on the aversive effects of cocaine, MDMA, and itself in adult, male Sprague-Dawley rats. Given eutylone's structural similarities with its parent compound methylone, it was predicted that its ability to attenuate cocaine- and MDMA-induced taste avoidance would parallel the effects of methylone pre-exposure in this design (cocaine > MDMA). In Experiment 1, male Sprague-Dawley rats were exposed to eutylone (20 mg/kg, IP) or equivolume saline every other day for five exposures followed by taste avoidance conditioning with 20 mg/kg cocaine (SC) or 1.8 mg/kg MDMA (SC). Both cocaine and MDMA induced significant taste avoidance that developed over repeated conditioning trials. Cocaine and MDMA-induced avoidance were unaffected by eutylone history. To assess the general ability of eutylone pre-exposure to attenuate taste avoidance conditioning in the pre-exposure design, in Experiment 2, an additional set of male Sprague-Dawley rats was injected with 20 mg/kg eutylone (IP) prior to taste avoidance conditioning with eutylone (20 mg/kg (IP). Under these conditions, eutylone-induced avoidance was attenuated by eutylone pre-exposure. Given that eutylone history attenuated eutylone-induced avoidance argues that the failure to affect cocaine or MDMA was not a function of eutylone in this preparation. The inability of eutylone to attenuate the aversive effects of cocaine and MDMA despite sharing pharmacological activity suggests that eutylone's hybrid pharmacology may create a unique interoceptive effect different than that produced by either drug.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 6
- Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation ACS Chemical Neuroscience March 9, 2021
- Effects of Serial Polydrug Use on the Rewarding and Aversive Effects of the Novel Synthetic Cathinone Eutylone Brain Sciences September 7, 2023
- Discriminative-Stimulus Effects of Synthetic Cathinones in Squirrel Monkeys The International Journal of Neuropsychopharmacology April 26, 2021
- Impact of fluoxetine preexposure on MDMA-induced taste avoidance in male and female rats. Experimental and Clinical Psychopharmacology November 17, 2022
- Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats: Implications for abuse vulnerability. Pharmacology, Biochemistry, and Behavior October 2022
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