Repeated exposure to 3,4-methylenedioxypyrovalerone and cocaine produces locomotor sensitization with minimal effects on brain monoamines

Abstract

Synthetic cathinones, known as "bath salts" on the illicit drug market, pose a significant public health concern. 3,4-Methylenedioxypyrovalerone (MDPV), one of several popular constituents of illicit bath salts, produces similar pharmacological actions to cocaine, albeit with greater potency and efficacy. The present study sought to characterize behavioral and neurochemical effects of repeated exposure to MDPV alone and in combination with cocaine. Male Sprague-Dawley rats were randomly assigned to one the following four treatments, administered once daily for seven days: 1 mg/kg MDPV, 5 mg/kg cocaine, 1 mg/kg MDPV +5 mg/kg cocaine, or saline. Locomotor activity was assessed for 1 h immediately before and 1 h immediately after injections on days 1 and 6. Brains were harvested 20 min after the final injection on day 7 and brain tissue punches were obtained to determine monoamine content within the anterior striatum, medial prefrontal cortex, and nucleus accumbens using High-Performance Liquid Chromatography (HPLC). Drug-induced increases in horizontal activity were significantly greater on treatment day 6 compared to treatment day 1 in all three drug treatment groups in comparison to the saline control group. MDPV produced significantly higher increases in activity compared to either saline or cocaine, although concurrent treatment with MDPV and cocaine produced sub-additive effects. Neurochemical analyses provided no evidence of alterations in total monoamine content following repeated administration of MDPV, cocaine, or the MDPV + COC mixture. Further investigations targeting possible changes in DA receptor sensitivity following repeated exposure to MDPV may help elucidate the mechanistic changes responsible for MDPV-induced behavioral sensitization. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

Keywords: Behavioral sensitization; Cocaine; Dopamine; Locomotor activity; MDPV; Medial prefrontal cortex; Monoamines; Nucleus accumbens; Rats; Serotonin; Striatum.