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


OBJECTIVE
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.
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2400; 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Shawn M
SM
Aarde
Kevin M
KM
Creehan
Sophia A
SA
Vandewater
Tobin J
TJ
Dickerson
Michael A
MA
Taffe
D000818:Animals; D052117:Benzodioxoles / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects; D015198:Designer Drugs / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010422:Pentanones / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D000094982:Synthetic Cathinone
D052117:Benzodioxoles; D015198:Designer Drugs; D010422:Pentanones; D011759:Pyrrolidines; C000592273:1-phenyl-2-(1-pyrrolidinyl)-1-pentanone; D000094982:Synthetic Cathinone