Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats

Bath salts preparations contain synthetic cathinones which interact with monoamine transporters and function as either monoamine uptake inhibitors or releasers. 3,4-Methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), and 4-methylmethcathinone (mephedrone) were three of the most common cathinones (i.e., first-generation cathinones); however, after the US Drug Enforcement Administration placed them under Schedule I regulations, they were replaced with structurally related cathinones that were not subject to regulations (i.e., second-generation cathinones). Although the reinforcing effects of some second-generation cathinones have been described (e.g., alpha-pyrrolidinopentiophenone [alpha-PVP]), little is known about how structural modifications, particularly those involving the methylenedioxy moiety and alpha-alkyl side chain, impact the abuse liability of other second-generation cathinones (e.g., alpha-pyrrolidinopropiophenone [alpha-PPP], 3,4-methylenedioxy-alpha-pyrrohdinobutiophenone [MDPBP], and 3,4-methylenedioxy-alpha-pyrrolidinopropiophenone [MDPPP]). The present study used male Sprague-Dawley rats (n = 12 per drug) to directly compare: (1) the acquisition of responding for alpha-PVP (0.032 mg/kg/inf), alpha-PPP (0.32 mg/kg/inf), MDPBP (0.1 mg/kg/inf), and MDPPP (0.32 mg/kg/inf) under a fixed ratio (FR) 1 schedule of reinforcement; and (2) full dose-response curves for each drug to maintain responding under an FR5 schedule of reinforcement. The average number of days (similar to 4 days) and percentage (100%) of rats that acquired self-administration was similar for each drug. The observed rank order potency to maintain responding under an FR5 schedule of reinforcement (alpha-PVP approximate to MDPBP>alpha-PPP > MDPPP) is consistent with their potencies to inhibit dopamine uptake. These are the first studies to report on the reinforcing effects of the unregulated second-generation cathinones MDPBP, MDPPP, and alpha-PPP and indicate all three compounds are readily self-administered, suggesting each possesses high potential for abuse. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'