Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats
PSYCHOPHARMACOLOGY
Authors: Bonano, J. S.; Glennon, R. A.; De Felice, L. J.; Banks, M. L.; Negus, S. S.
Abstract
Abuse of synthetic cathinones, popularized as "bath salts," has increased dramatically in the USA since their debut in 2010. Preclinical behavioral studies may clarify determinants of the abuse-related effects produced by these compounds. This study examined behavioral effects of (+/-)-methcathinone, (+/-)-3,4-methylenedioxypyrovalerone (MDPV), (+/-)-3,4-methylenedioxymethcathinone (methylone), and (+/-)-4-methylmethcathinone (mephedrone) in rats using intracranial self-stimulation (ICSS). Male Sprague-Dawley rats (n = 18) with electrodes targeting the medial forebrain bundle responded for multiple frequencies of brain stimulation and were tested in two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg), MDPV (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg) were determined. Second, time courses were determined for effects produced by the highest dose of each compound. Methcathinone produced dose- and time-dependent facilitation of ICSS. MDPV, methylone, and mephedrone produced dose- and time-dependent increases in low rates of ICSS maintained by low brain stimulation frequencies, but also produced abuse-limiting depression of high ICSS rates maintained by high brain stimulation frequencies. Efficacies to facilitate ICSS were methcathinone a parts per thousand yen MDPV a parts per thousand yen methylone > mephedrone. Methcathinone was the most potent compound, and MDPV was the longest acting compound. All compounds facilitated ICSS at some doses and pretreatment times, which is consistent with abuse liability for each of these compounds. However, efficacies of compounds to facilitate ICSS varied, with methcathinone displaying the highest efficacy and mephedrone displaying the lowest efficacy to facilitate ICSS.
Effects of 3,4-methylenedioxypyrovalerone (MDPV) pre-exposure on the aversive effects of MDPV, cocaine and lithium chloride: Implications for abuse vulnerability
DRUG AND ALCOHOL DEPENDENCE
Authors: Woloshchuk, Claudia J.; Nelson, Katharine H.; Rice, Kenner C.; Riley, Anthony L.
Abstract
Background: Drug use is thought to be a balance of the rewarding and aversive effects of drugs. Understanding how various factors impact these properties and their relative balance may provide insight into their abuse potential. In this context, the present study attempted to evaluate the effects of drug history on the aversive effects of 3,4-methylenedioxypyrovalerone (MDPV), one of a variety of synthetic cathinones (collectively known as "bath salts"). Methods: Different groups of male Sprague-Dawley rats were exposed to either vehicle or MDPV (1.8 mg/kg) once every fourth day for five total injections prior to taste avoidance conditioning in which a novel saccharin solution was repeatedly paired with either vehicle, MDPV (1.8 mg/kg), the related psychostimulant cocaine (18 mg/kg) or the emetic lithium chloride (LiCl) (13.65 mg/kg). Results: In animals pre-exposed to vehicle, all three drugs induced significant and comparable taste avoidance relative to animals injected with vehicle during conditioning. MDPV pre-exposure attenuated the avoidance induced by both MDPV and cocaine (greater attenuation for MDPV than cocaine), but had no effect on that induced by LiCl. Conclusions: These findings suggest that a history of MDPV use may reduce or attenuate MDPV and cocaine's (but not Lid 's) aversive effects. The implications for such changes in MDPV's aversive effects to its potential use and abuse were discussed. (C) 2016 Elsevier Ireland Ltd. All rights reserved.