Reinforcing effects of abused 'bath salts' constituents 3,4-methylenedioxypyrovalerone and α-pyrrolidinopentiophenone and their enantiomers

Abstract

Synthetic cathinones found in abused 'bath salts' preparations are chiral molecules. Racemic 3,4-methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (α-PVP) are two common constituents of these preparations that have been reported to be highly effective reinforcers; however, the relative contribution of each enantiomer toward these effects has not been determined. Thus, male Sprague-Dawley rats were trained to respond for racemic MDPV or α-PVP (n=9/drug), with full dose-response curves for the racemate and the S and R enantiomers of MDPV and α-PVP generated under a progressive ratio schedule of reinforcement. Racemic mixtures of both MDPV and α-PVP as well as each enantiomer maintained responding in a dose-dependent manner, with racemic MDPV and α-PVP being equipotent. The rank order of potency within each drug was S enantiomer>racemate ≫ R enantiomer. Although both enantiomers of α-PVP were as effective as racemic α-PVP, R-MDPV was a slightly less effective reinforcer than both S and racemic MDPV. The results of these studies provide clear evidence that both enantiomers of MDPV and α-PVP function as highly effective reinforcers and likely contribute toward the abuse-related effects of 'bath salts' preparations containing racemic MDPV and/or α-PVP.

Figure 1

Dose-response curves for the self-administration of racemic (circles), S- (squares), and R-(triangles) MDPV (left panel) or α-PVP (right panel) under a progressive ratio schedule of reinforcement. Horizontal axis: SAL represents data obtained when saline was available for infusion, whereas numbers refer to the unit dose of each drug available for infusion expressed as mg/kg/inf on a log scale. Vertical axis: Left- Total infusions obtained during the session. Right- Final ratio completed during the session. Symbols and error bars depict means ± S.E.M.