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

• Published in: Neuropharmacology Vol. 134; no. Pt A; pp. 28 - 35
• Main Authors: Gannon, Brenda M., Galindo, Kayla I., Mesmin, Melson P., Sulima, Agnieszka, Rice, Kenner C., Collins, Gregory T.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.05.2018
• Subjects: Analysis of Variance; Animals; Bath salts; Benzodioxoles - chemistry; Benzodioxoles - pharmacology; Conditioning, Operant - drug effects; Designer Drugs - chemistry; Designer Drugs - pharmacology; Dopamine transporter; Dose-Response Relationship, Drug; Inhibitory Concentration 50; Male; MDPBP; MDPPP; Methamphetamine - analogs & derivatives; Methamphetamine - chemistry; Methamphetamine - pharmacology; Pyrrolidines - chemistry; Pyrrolidines - pharmacology; Rats; Rats, Sprague-Dawley; Reinforcement (Psychology); Reinforcement Schedule; Self Administration; Synthetic cathinones; α-PPP; α-PVP; Self-administration; MDPPP; α-PVP; Synthetic cathinones; Dopamine transporter; MDPBP; Bath salts; α-PPP
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2017.08.018

“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., α-pyrrolidinopentiophenone [α-PVP]), little is known about how structural modifications, particularly those involving the methylenedioxy moiety and α-alkyl side chain, impact the abuse liability of other second-generation cathinones (e.g., α-pyrrolidinopropiophenone [α-PPP], 3,4-methylenedioxy-α-pyrrolidinobutiophenone [MDPBP], and 3,4-methylenedioxy-α-pyrrolidinopropiophenone [MDPPP]). The present study used male Sprague-Dawley rats (n = 12 per drug) to directly compare: (1) the acquisition of responding for α-PVP (0.032 mg/kg/inf), α-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 (∼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 (α-PVP ≈ MDPBP>α-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 α-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.’ •Self-administration of the structurally related synthetic cathinones MDPBP, MDPPP, α-PVP, and α-PPP was rapidly acquired.•Responding for MDPBP, MDPPP, α-PVP, and α-PPP was maintained over a range of doses.•The potency of each drug to reinforce responding was related to its potency to inhibit dopamine uptake.