Discriminative Stimulus Effects of Mephedrone, A Constituent of “Bath salts”

Abstract

Mephedrone (4‐methylmethcathinone) is one of the major constituents of the recreational substances known as “bath salts”. It is a synthetic cathinone and psychostimulant that has been reported to cause auditory and visual hallucinations, as well as problematic cardiovascular effects. The purpose of this study was to compare the discriminative stimulus effects of mephedrone (0.32–10 mg/kg) alone with other prototypical drugs of abuse, such as cocaine (0.56–32 mg/kg), delta‐9‐tetrahydrocannabinol (THC, 0.56–10 mg/kg), ketamine (1.8–18 mg/kg), phencyclidine (PCP, 1–5.6 mg/kg), 2,5‐dimethoxy‐4‐iodoamphetamine (R‐DOI, 0.1‐1 mg/kg), heroin (1–10 mg/kg) and d‐amphetamine (0.18–3.2 mg/kg). The discriminative stimulus effects of mephedrone were also examined after the administration of rimcazole (0.32–10 mg/kg), a sigma receptor antagonist, and desipramine (1.8–18 mg/kg), a tricyclic antidepressant with relatively selective affinity for norepinephrine transporters (NET). Rats were trained to discriminate an intraperitoneal injection of mephedrone from saline under a fixed‐ratio 20 schedule of food presentation. The training dose of mephedrone (3.2 mg/kg) was reliably discriminated from saline by all subjects. Following training, substitution of varying doses of mephedrone produced dose‐dependent increases in mephedrone‐lever responding, with full substitution considered to be greater than 80% responding on this lever. Of the drugs tested, only cocaine and THC fully substituted for mephedrone. However, full substitution of THC occurred in only 2 of 9 animals and at a dose that substantially decreased response rate. Both THC and R‐DOI produced dose‐dependent rate‐decreasing effects (≥ 20% decrease in response rate compared to vehicle). In addition, although rimcazole and desipramine did not substitute for mephedrone, both drugs potentiated mephedrone's discriminative stimulus effects by producing leftward shifts of the dose‐effect curve for mephedrone‐lever responding. In summary, the discriminative stimulus effects of mephedrone most closely approximate those for the stimulant, cocaine, and these effects may be mediated, in part, by the sigma receptor and NET.