Locomotor and reinforcing effects of pentedrone, pentylone and methylone in rats

NEUROPHARMACOLOGY

卷:134

Article

Javadi-Paydar, Mehrak¹  Nguyen, Jacques D.¹  Vandewater, Sophia A.¹  Dickerson, Tobin J.²  Taffe, Michael A.¹ 

[1] Scripps Res Inst, Dept Neurosci, SP30-2400,10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

关键词: Self-administration;    Psychostimulant;    Reward;    Locomotor activity;   

DOI  :  10.1016/j.neuropharm.2017.09.002

来源: Elsevier

【 摘 要 】

The broad diversity of synthetic cathinone psychostimulant drugs that are available to users complicates research efforts to provide understanding of health risks. Second generation cathinones pentedrone and pentylone are distinguished from each other by the 3,4-methylenedioxy structural motif (which distinguishes methamphetamine from 3,4-methylenedioxymethamphetamine) and each incorporates the a-alkyl chain motif contained in the transporter-inhibitor cathinones (3,4-methylenedioxypyrovalerone (MDPV), alpha-pyrrolidinopentiophenone (alpha-PVP)) but not in the monoamine releasers (mephedrone, methylone). Studies were conducted in male and female Wistar rats to compare locomotor and thermoregulatory effects of pentedrone, pentylone and methylone using an implanted radiotelemetry system. Reinforcing effects were assessed in female Wistar rats trained in the intravenous selfadministration (IVSA) procedure and subjected to dose-substitution (0.025-0.3 m/gkg/inf) under a fixed-ratio 1 response contingency. Pentedrone, pentylone and methylone dose-effect curves were contrasted with those for alpha-PVP and alpha-pyrrohdmohexiophenone (alpha-PHP). Dose dependent increases in locomotion were observed after intraperitoneal injection of pentylone (0.5-10.0 mg/kg), pentedrone (0.5 -10.0 mg/kg) or mephedrone (0.5-10.0 mg/kg) in male and female rats. The maximum locomotor effect was similar across drugs but lasted longest after pentedrone. Mean body temperature did not vary systematically more than 0.5 degrees C after pentedrone or pentylone in either sex. A sustained hyperthermia (0.4-0.8 degrees C) was observed for four hours after 10.0 mg/kg methylone in male rats. More infusions of pentedrone or pentylone were self-administered compared with methylone, but all three were less potent than alpha-PVP or alpha-PHP. These studies support the inference that second generation cathinones pentylone and pentedrone have abuse liability greater than that of methylone. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

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