Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats

Exceedingly little experimental research exists on the popular recreational drug mephedrone (4-methylmethcathinone) despite clinical reports concerning its behavioral and cardiovascular toxicity. To characterize mephedrone preclinically by examining its capacity to (1) serve as a discriminative stimulus, (2) disrupt the acquisition of response sequences, and (3) disrupt mean arterial pressure (MAP) and heart rate (HR). In one group of subjects that reliably discriminated 3.2 mg/kg of mephedrone from saline (n = 9), substitution tests indicated that stimulants (cocaine, MDMA, and methamphetamine) more closely approximated the mephedrone discriminative stimulus than non-stimulants (fenfluramine, morphine, and phencyclidine), although none fully substituted. In a second group (n = 6), mephedrone (0.56-10 mg/kg, i.p.) dose-dependently decreased response rate and increased errors in both components of a procedure in which subjects either acquired a new response sequence each session (repeated acquisition) or completed the same response sequence each session (performance). Finally, in a third group (n = 12), radio telemetry probes were used to measure the changes in MAP and HR elicited by mephedrone and then compared them to a known stimulant, methamphetamine. In these studies, mephedrone (0.01-9 mg/kg, i.v.) elicited increases in MAP and HR that were very similar to those elicited by methamphetamine (0.01-9 mg/kg, i.v.). The tachycardia and pressor responses to mephedrone (3 mg/kg) were blocked by the beta-blocker atenolol (1 mg/kg, i.v.) and the alpha 1, alpha 2-blocker phentolamine (3 mg/kg, i.v.), respectively. Mephedrone produces behavioral and cardiovascular responses that are similar to other stimulants; however, differences from the classical stimulants were also apparent.