Mephedrone (4-methylmethcathinone) and intracranial self-stimulation in C57BL/6J mice: Comparison to cocaine

► Mephedrone and cocaine similarly affected ICSS responding in C57BL/6J mice. ► Both drugs decreased the EF50 and BSR threshold (θ0). ► 10.0mg/kg mephedrone (i.p.) lowered maximum operant response rate. ► Mephedrone had a slower onset of action than cocaine. The recreational use of cathinone-derived synthetic stimulants, also known as “bath salts”, has increased during the last five years. A commonly abused drug in this class is mephedrone (4-methylmethcathinone or “meow–meow”), which alters mood and produces euphoria in humans. Intracranial self-stimulation (ICSS) measures the behavioral effects of neuroactive compounds on brain reward circuitry. We used ICSS to investigate the ability of mephedrone and cocaine to alter responding for electrical stimulation of the medial forebrain bundle in C57BL/6J mice. Adult male C57BL/6J mice (n=6) implanted with unipolar stimulating electrodes at the level of the lateral hypothalamus responded for varying frequencies of brain stimulation reward (BSR). The frequency that supported half maximal responding (EF50), the BSR threshold (θ0), and the maximum response rate were determined before and after intraperitoneal administration of saline, mephedrone (1.0, 3.0, or 10.0mg/kg), or cocaine (1.0, 3.0, or 10.0mg/kg). Mephedrone dose-dependently decreased EF50 (max. effect=72.3% of baseline), θ0 (max. effect=59.6% of baseline), and the maximum response rate (max. effect=67.0% of baseline) beginning 15min after administration. Beginning immediately after administration, cocaine dose-dependently lowered EF50 (max. effect=66.4% of baseline) and θ0 (max. effect=60.1% of baseline) but did not affect maximum response rate. These results suggest that mephedrone, like cocaine, potentiates BSR, which may indicate its potential for abuse. Given the public health concern of stimulant abuse, future studies will be necessary to determine the cellular and behavioral effects of acute and chronic mephedrone use.