Ethanol pre-exposure differentially impacts the rewarding and aversive effects of α-pyrrolidinopentiophenone (α-PVP): Implications for drug use and abuse

Abstract

RATIONALE\nExposure to a drug can subsequently impact its own reactivity as well as that of other drugs. Given that synthetic cathinones, i.e., bath salts , users typically have extensive and varied drug histories, an understanding of the effects of drug history on its behavioral and physiological effects may be important to its abuse liability.\n\n\nOBJECTIVES\nThe goal of the current work was to assess the effects of an ethanol pre-exposure on the rewarding and aversive effects of α-PVP.\n\n\nMETHODS\nAdult male Sprague Dawley rats were exposed to ethanol prior to combined conditioned taste avoidance/conditioned place preference training in which rats were injected with 1.5, 3 or 5\u202fmg/kg of racemic α-PVP or vehicle. Following a 7-day washout period, rats were then tested for thermoregulatory effects of α-PVP using subcutaneous probes to measure body temperature changes over the course of 8\u202fh. This was followed 10\u202fdays later by assessments for α-PVP-induced locomotor activity and stereotypies over a 1-h session.\n\n\nRESULTS\nα-PVP induced significant dose- and trial-dependent taste avoidance that was significantly attenuated by ethanol history and dose- and time-dependent increases in locomotor activity that were significantly increased by ethanol. α-PVP also induced place preferences and dose- and time-dependent increases in body temperature, but these measures were unaffected by ethanol history.\n\n\nCONCLUSIONS\nα-PVP s aversive effects (as measured by taste avoidance) were attenuated, while its rewarding effects (as indexed by place preference conditioning) were unaffected, by ethanol pre-exposure. Such a pattern may indicate increased α-PVP abuse liability, as changes in the balance of aversion and reward may impact overall drug effects and likelihood of drug intake. Future self-administration studies will be necessary to explore this possibility.