Effects of SCH‐23390 and Alpha‐Methyl‐Tyrosine on the Discriminative Stimulus Effects of Mephedrone in Male Rats

Abstract

The illicit synthetic cathinone mephedrone (4‐methylmethcathinone) often termed a “bath salt” produces discriminative stimulus effects that are similar, but not identical, to those for central nervous system stimulants such as cocaine and methamphetamine. This may be due to its capacity to bind atypically at both dopamine and serotonin transporters compared to those drugs. The purpose of the present study was to further elucidate the mechanism of action underlying mephedrone’s discriminative stimulus effects by administering it with the dopamine type‐1 receptor antagonist SCH‐23390 (n=11) or the catecholamine synthesis inhibitor alpha‐methyl‐tyrosine (alpha‐MT; n=8). Male Long‐Evans rats were trained to discriminate intraperitoneal injections of mephedrone (3.2 mg/kg) from saline under a fixed‐ratio 20 (FR‐20) schedule of food presentation. Mephedrone dose‐effect curves (0.32 – 10 mg/kg) were then established by administering increasing cumulative doses of mephedrone on test days, and comparing those effects with multiple (4–5) injections of saline. The interaction of SCH‐23390 (0.032 – 0.1 mg/kg) and alpha‐MT (200 mg/kg) with mephedrone was examined by administering an acute injection of these drugs prior to increasing cumulative doses of mephedrone. As shown previously by our laboratory, saline administration produced almost exclusively saline‐lever responding while increasing cumulative doses of mephedrone dose‐dependently increased mephedrone‐lever responding. When SCH‐23390 preceded cumulative doses of mephedrone, neither dose alone produced mephedrone‐lever responding and only the larger of the two doses tested (0.1 mg/kg) shifted the mephedrone dose‐effect curve rightward; however, this shift was still less than 2‐fold and produced rate‐decreasing effects when administered alone. Acute administration of alpha‐MT alone also did not produce mephedronelever responding nor decrease rate, and in combination did not produce a marked rightward shift in the mephedrone dose‐effect curve. Taken together, these data indicate that neither SCH‐23390 nor alpha‐MT effectively antagonize the discriminative stimulus effects of mephedrone, and the alpha‐MT data in particular suggest that mephedrone’s discriminative stimulus effects do not depend on newly synthesized catecholamines.