Neurochemical Outcomes Following Individual and Combined Synthetic Cathinone Exposure

Abstract

Synthetic cathinones, marketed as ‘bath salts’, are an emerging class of highly addictive designer drugs that can precipitate dangerous health effects when abused. DEA statistics and case reports indicate the three most commonly abused cathinones, 3, 4‐methylenedioxypyrovalerone (MDPV), 4‐methylmethcathinone (mephedrone), and 3, 4‐methylenedioxymethcathinone (methylone), are frequently found in combination with each other or with other illicit substances. Previous findings indicate that synthetic cathinones have analogous pharmocology to cocaine, the amphetamines, and MDMA. While much of the current ‘bath salt’ research has focused on elucidating the individual drug mechanisms, this study aimed to determine the individual and combined effects of MDPV, mephedrone, and methylone on monoaminergic tone in various brain regions. For this study, Swiss‐Webster mice were administered saline (control) or MDPV, mephedrone, or methylone individually or in combination at both low (1mg/kg) and high (10mg/kg) doses. Four groups were examined for each dose: 1) Acute individual cathinones; 2) Acute combined cathinones; 3) Chronic individual cathinones; 4) Chronic combined cathinones, and the following brain regions were collected from each mouse: frontal cortex (FCTX), striatum (STR), nucleus accumbens (NAC), hippocampus (HIP), substantia nigra (SN), and ventral tegmental area (VTA). High performance liquid chromatography (HPLC) equipped with electrochemical detection (ECD) was utilized to measure tissue concentrations of of monoamines (DA, NE, 5‐HT) and their metabolites (DOPAC, HVA, and 5‐HIAA). A number of differences were noted amongst the groups. Generally, acute individual exposure to cathinones (group 1) increased DA, NE, 5‐HT levels and decreased DA and 5‐HT turnover in certain brain regions, and a dose‐response relationship was observed. Following acute administration of MDPV, mephedrone, and methylone in combination (group 2), similar increases in monoamine levels and decreases in DA and 5‐HT turnover were observed, but in many regions, the combination treatment showed an additive effect (greater decreases in turnover compared to individual cathinones). Interestingly, chronic exposure to individual cathinones (group 3) appeared to have the opposite effect, decreasing monoamine levels and increasing DA and 5‐HT turnover in certain regions; however, while chronic combination treatment appeared to increase turnover as well, it did so to a lesser extent than individual chronic cathinone treatment. Taken together, these data suggest that synthetic cathinones individually function to decrease DA turnover within the brain reward pathway when delivered acutely and to increase both DA turnover and 5‐HT turnover in major serotonergic and dopaminergic targets, respectively, following chronic exposure. These data also suggest that combined administration of these drugs may intensify their associated neurochemical effects via a sustained increase in DA and 5‐HT in various brain regions.Support or Funding InformationThis project was supported by the Department of Pharmaceutical Sciences at the East Tennessee State University Bill Gatton College of Pharmacy.