Effects of the Long-Acting Monoamine Reuptake Inhibitor Indatraline on Cocaine Self-Administration in Rhesus Monkeys1

Abstract

Cocaine is a nonselective monoamine reuptake inhibitor that is widely abused. Useful pharmacotherapies for cocaine dependence may include substitution medications that produce cocaine-like effects but have a slower onset and longer duration of action. Accordingly, the present study examined the effects of the long-acting, nonselective monoamine reuptake inhibitor indatraline in assays of cocaine discrimination and cocaine self-administration that have been used to evaluate other candidate treatment medications. In rhesus monkeys trained to discriminate cocaine (0.4 mg/kg) from saline, indatraline (0.1–1.0 mg/kg) produced a dose- and time-dependent substitution for cocaine. The effects of 1.0 mg/kg indatraline peaked after 30 min and lasted up to 24 h. In monkeys trained to self-administer 0.032 mg/kg/injection cocaine and food pellets during alternating daily sessions of cocaine and food availability, indatraline (0.0032–0.032 mg/kg/injection) maintained lower rates of responding than cocaine. Repeated treatments with indatraline (0.1–0.56 mg/kg/day) for 7 days produced dose-dependent and sustained decreases in cocaine self-administration across a broad range of cocaine doses (0.0032–0.1 mg/kg/injection), and the highest dose of indatraline (0.56 mg/kg/day) nearly eliminated cocaine-maintained responding. However, doses of indatraline that decreased cocaine self-administration also usually decreased rates of food-maintained responding and produced behavioral stereotypies and trends toward weight loss and mild anemia. These findings suggest that although indatraline may decrease cocaine-taking behavior in rhesus monkeys, it also produces undesirable side effects that may limit its clinical utility in the treatment of cocaine dependence.