Exploring the pharmacologic and discriminative effects of abused psychostimulants and the bath salt component mephedrone in rats

Abstract

The underlying mechanisms of both commonly abused and novel psychostimulants such as mephedrone are still a critical area of study. Comparing mephedrone to other more well‐known drugs in an established drug discrimination protocol allows for increased understanding of their pharmacological profiles and potential abuse liabilities. We hypothesize that mephedrone exhibits mixed pharmacology with low doses having a primarily serotonergic mechanism, and higher doses having a primarily dopaminergic mechanism. Male Sprague‐Dawley rats were trained using two‐choice drug discrimination assays to examine the stimulus properties of either a low dose of 0.5 mg/kg mephedrone (n=12) vs saline or a high dose of 3.2 mg/kg mephedrone vs saline (n=11). Rats learned the low and high dose discriminations in 74 and 175 sessions, respectively. Current results show that mephedrone substitutes in a dose‐dependent fashion in both groups, although with different potencies. In the low dose cohort, dopamine (DA) agonists (cocaine and D‐amphetamine) partially substitute for mephedrone whereas methamphetamine fully substitutes. However, we did not see full substitution of the aforementioned DA agonists in the high mephedrone training dose group. The serotonergic agonist (2,5‐Dimethoxy‐4‐iodoamphetamine or DOI) in moderate to high doses (0.5 to 1.0 mg/kg) partially substituted for both high and low doses of mephedrone. In conclusion, mephedrone appears to mimic pharmacological properties similar to other psychostimulants that possess dual DA and 5‐HT mechanisms and the high dose mephedrone training dose cohort may be less sensitive to DA activation than the low dose cohort. Further analysis will focus more on the susceptibility of mephedrone to DA and 5‐HT antagonism.Support or Funding InformationSupported by R21DA032718