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Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats.
Neuropharmacology. 2018 05 15; 134(Pt A):28-35.N

Abstract

"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.'

Authors+Show Affiliations

Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852, USA.Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20852, USA.Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; South Texas Veterans Health Care System, San Antonio, TX 78229, USA. Electronic address: CollinsG@uthscsa.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

28811192

Citation

Gannon, Brenda M., et al. "Relative Reinforcing Effects of Second-generation Synthetic Cathinones: Acquisition of Self-administration and Fixed Ratio Dose-response Curves in Rats." Neuropharmacology, vol. 134, no. Pt A, 2018, pp. 28-35.
Gannon BM, Galindo KI, Mesmin MP, et al. Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats. Neuropharmacology. 2018;134(Pt A):28-35.
Gannon, B. M., Galindo, K. I., Mesmin, M. P., Sulima, A., Rice, K. C., & Collins, G. T. (2018). Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats. Neuropharmacology, 134(Pt A), 28-35. https://doi.org/10.1016/j.neuropharm.2017.08.018
Gannon BM, et al. Relative Reinforcing Effects of Second-generation Synthetic Cathinones: Acquisition of Self-administration and Fixed Ratio Dose-response Curves in Rats. Neuropharmacology. 2018 05 15;134(Pt A):28-35. PubMed PMID: 28811192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relative reinforcing effects of second-generation synthetic cathinones: Acquisition of self-administration and fixed ratio dose-response curves in rats. AU - Gannon,Brenda M, AU - Galindo,Kayla I, AU - Mesmin,Melson P, AU - Sulima,Agnieszka, AU - Rice,Kenner C, AU - Collins,Gregory T, Y1 - 2017/08/12/ PY - 2017/05/18/received PY - 2017/08/08/revised PY - 2017/08/10/accepted PY - 2017/8/16/pubmed PY - 2018/11/8/medline PY - 2017/8/17/entrez KW - Bath salts KW - Dopamine transporter KW - MDPBP KW - MDPPP KW - Self-administration KW - Synthetic cathinones KW - α-PPP KW - α-PVP SP - 28 EP - 35 JF - Neuropharmacology JO - Neuropharmacology VL - 134 IS - Pt A N2 - "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.' SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/28811192/Relative_reinforcing_effects_of_second_generation_synthetic_cathinones:_Acquisition_of_self_administration_and_fixed_ratio_dose_response_curves_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(17)30385-4 DB - PRIME DP - Unbound Medicine ER -