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In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats.

Abstract：

RATIONALE:Numerous substituted cathinone drugs have appeared in recreational use. This variety is often a response to legal actions; the scheduling of 3,4-methylenedioxypyrovalerone (MDPV; "bath salts") in the USA was followed by the appearance of the closely related drug α-pyrrolidinopentiophenone (alpha-PVP; "flakka"). OBJECTIVES:This study aimed to directly compare the efficacy and potency of alpha-PVP with that of MDPV. METHODS:Groups of male Wistar rats were trained in the intravenous self-administration (IVSA) alpha-PVP or MDPV under a fixed-ratio 1 schedule of reinforcement. An additional group was examined for locomotor and body temperature responses to noncontingent administration of MDVP or alpha-PVP (1.0, 5.6, and 10.0 mg/kg, i.p.). RESULTS:Acquisition of alpha-PVP (0.1 mg/kg/infusion) IVSA resulted in low, yet consistent drug intake and excellent discrimination for the drug-paired lever. Dose substitution (0.05-0.25 mg/kg/infusion) under a fixed-ratio 1 schedule confirmed potency was similar to MDPV in prior studies. In direct comparison to MDPV (0.05 mg/kg/infusion), rats trained on alpha-PVP (0.05 mg/kg/infusion) responded for more infusions but demonstrated similar drug-lever discrimination by the end of acquisition. However, the dose-response (0.018-0.56 mg/kg/infusion) functions of these drugs under a progressive-ratio schedule of reinforcement reflected identical efficacy and potency. Peak locomotor responses to MDPV or alpha-PVP were observed after the 1.0 mg/kg, i.p. dose and lasted ∼2 h. Modest body temperature decreases were of similar magnitude (∼0.75 °C) for each compound. CONCLUSIONS:The potency and efficacy of MDPV and alpha-PVP were very similar across multiple assays, predicting that the abuse liability of alpha-PVP will be significant and similar to that of MDPV.

journal_name

Psychopharmacology (Berl)

journal_title

Psychopharmacology

authors

Aarde SM,Creehan KM,Vandewater SA,Dickerson TJ,Taffe MA

doi

10.1007/s00213-015-3944-8

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

3045-55

issue

eissn

0033-3158

issn

1432-2072

journal_volume

232

pub_type

杂志文章

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In vivo potency and efficacy of the novel cathinone α-pyrrolidinopentiophenone and 3,4-methylenedioxypyrovalerone: self-administration and locomotor stimulation in male rats.