Dose Effects of Synthetic Cathinone Mephedrone on Cocaine Reinstatement in Rats

Abstract

Mephedrone is a recreational synthetic cathinone and a major component of psychoactive ‘bath salts.’ In previous in vitro studies, mephedrone increases dopamine (DA) and serotonin (5‐HT) release and inhibits DA and 5‐HT synaptosomal uptake similar to other abused stimulants.The purpose of this study was to determine the capacity of mephedrone to reestablish on cocaine self‐administration when a history of cocaine is already established in rats. We predict that rats will readily engage in cocaine‐seeking behavior after the extinction of cocaine self‐administration, when presented with a mephedrone‐induced prime injection. If mephedrone activates the mesolimbic DA system and produces a rewarding effect through DA mechanisms, then mephedrone will reinstate the extinguished cocaine‐seeking behavior in a pattern comparable to cocaine. Male Sprague‐Dawley rats were allowed to self‐administer 0.375 mg/kg/inf of cocaine for two hours for a total of 10–14 days. Following 8–20 days of extinction, rats were reinstated with either i.p. injection of 10 mg/kg cocaine, 1, 5, or 10 mg/kg mephedrone.After acquisition and extinction, a high dose of 10.0 mg/kg cocaine produced reinstatement of cocaine‐responding. A moderate dose of 5.0 mg/kg mephedrone decreased amount of infusions administered during reinstatement. However, a low and high dose of 1.0 and 10.0 mg/kg mephedrone produced an increased amount of infusions, but not higher than cocaine. In addition, only 4 rats failed to reinstate cocaine responding after cocaine‐prime but 10 rats failed to reinstate after any dose of mephedrone‐prime. These preliminary results suggest that after a history of cocaine self‐administration, cocaine reinstates cocaine responding more fully than mephedrone. This may be due to mephedrone's dual dopaminergic and serotonergic mechanism.