Cocaine Enhances the Discriminative Stimulus Effects of Mephedrone

Mephedrone (4‐methylmethcathinone) is one of the major constituents of “bath salts.” It is a drug with discriminative effects similar to CNS stimulants and it can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32–10 mg/kg) with other prototypical drugs with CNS effects, such as ketamine (1.8–18 mg/kg), bupropion (5.6–56 mg/kg), and 3,4‐methylenedioxyamphetamine (MDA) (0.32–5.6 mg/kg). In addition, mephedrone was administered in combination with cocaine (5.6–32 mg/kg), which inhibits the reuptake of catecholamines and serotonin. Rats (n=6) were trained to discriminate an intraperitoneal injection of 3.2 mg/kg mephedrone from saline under a fixed‐ratio 20 schedule. Following training, increasing cumulative doses of mephedrone produced dose‐dependent increases in mephedrone‐lever responding, with full substitution considered to be greater than 80% responding and partial substitution to be greater than 50% responding. During substitution tests, ketamine never produced more than 17% drug‐lever responding up to doses that significantly decreased overall response rate. In addition, bupropion and MDA produced 36% and 77% drug‐lever responding, respectively, without significantly decreasing response rate. When 3.2 mg/kg of cocaine was administered prior to increasing doses of mephedrone, there was no substitution for cocaine alone; however, this dose produced a rightward shift in the dose‐effect curve for mephedrone‐lever responding. Unlike this dose, 5.6 mg/kg of cocaine alone did not substitute for mephedrone or shift the mephedrone dose‐effect curve. When the dose of cocaine was increased to 10 mg/kg, there was still no mephedrone substitution, but this dose increased the mephedrone‐lever responding of the low doses of mephedrone. Finally, 18 and 32 mg/kg of cocaine produced 38.1% and 77.7% substitution, respectively, and dose‐dependently increased the substitution of the low doses of mephedrone (0.32 – 1.8 mg/kg). This data suggest that mephedrone may be similar to cocaine in having a higher affinity for the serotonin transorter (SERT) than the dopamine transporter (DAT), but more efficacy at DAT than SERT. Certainly, due to the capacity of cocaine to only enhance the substitution of the low mephedrone doses, the discriminative stimulus effects of the training dose of mephedrone are mediated predominately by dopamine rather than serotonin. Support or Funding Information This research was supported by the Louisiana Board of Regents Fellowship. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .