Conditioned taste avoidance and conditioned place preference induced by the third-generation synthetic cathinone eutylone in female sprague-dawley rats.

Abstract

Recently, use of the synthetic cathinone (aka "bath salt") eutylone has risen in the United States and globally. Due to its novelty in drug markets, its affective properties remain largely uninvestigated. In this context, drugs of abuse have both rewarding and aversive effects and understanding these effects, their relative balance, and factors that impact each are important to understanding the likelihood of drug use and abuse. This investigation attempted to characterize eutylone's rewarding and aversive effects in a combined conditioned taste avoidance/place preference assay. Female Sprague-Dawley rats were given 20-min access to saccharin, injected with one of five doses of eutylone (0, 3, 10, 18, 32 mg/kg; intraperitoneally; IP), and placed on one side of a place conditioning apparatus. On the following day, subjects were given 20-min access to water, injected IP with vehicle, and placed on the other side of the apparatus. After five conditioning cycles, place preference and saccharin avoidance were assessed. Eutylone induced significant taste avoidance but did not significantly increase time spent on the drug-paired side (relative to controls). Excluding animals with high initial side preference, however, eutylone induced a preference at all doses with the high dose group displaying higher preference than controls. There was no significant correlation between eutylone's aversive and rewarding effects. These data indicate that eutylone (like other synthetic cathinones) induces both rewarding and aversive effects and highlight the need to assess the impact of various factors on its affective properties (and their balance) and on their use and abuse. Public Health SignificanceThis study is the first to demonstrate taste avoidance and place preference induced by the novel synthetic cathinone eutylone. Given that a drug's aversive and rewarding effects are thought in balance to mediate its use and abuse, the present study indicates the potential abuse of eutylone and the importance in assessing various factors that could affect this liability.

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

“…Eutylone induced significant dose-dependent CTA (at 10 and 32 mg/kg) and CPP (at 3.2 and 32 mg/kg), and these effects were not correlated indicating they are independent and dissociable. The fact that eutylone was effective in induced taste avoidance and place preference conditioning is consistent with prior work with rats (although avoidance was stronger in rats than mice, effects consistent with other work in which mice and rats have been compared; see [48,[66][67][68][69]; see below). Although there are few studies that have examined the relationship between taste avoidance and place preference, the data that have been collected appear to be mixed.…”

“…The rewarding and aversive effects and their dissociation reported above are consistent with other drugs of abuse (for a review, see [7,9]), including synthetic cathinones [48,69,72]. Given the data demonstrating effective doses of eutylone in taste and place conditioning, Experiment 2 assessed the potential interaction of compounds neurochemically related to eutylone.…”

“…Further, this suggests that the mouse does not defend deprivation as well as the rat (for which most of the work on one- and two-bottle assessments have been made). Mice appear not to be able to suppress consumption as effectively as rats which is interesting in the light of the fact that for a host of drugs (including eutylone), mice display significant weaker taste avoidance than rats [ 48 , 66 , 67 , 68 , 69 ], suggestive that although the drug may be aversive (as one can see with higher doses), deprivation may limit their ability to suppress consumption in general. This is speculation, but such an interpretation has been given to other subject manipulations (e.g., sex difference comparisons; see [ 121 , 122 ]).…”

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

“…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].…”