Effects of the long-acting monoamine reuptake inhibitor indatraline on cocaine self-administration in rhesus monkeys

Cocaine is a nonselective monoamine reuptake inhibitor that is widely abuse d. 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 effe cts of the long-acting, nonselective monoamine reuptake inhibitor indatrali ne in assays of cocaine discrimination and cocaine self-administration that have been used to evaluate other candidate treatment medications. In rhesu s monkeys trained to discriminate cocaine (0.4 mg/kg) from saline, indatral ine (0.1-1.0 mg/kg) produced a dose- and time-dependent substitution for co caine. 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 coc aine 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 (0.00 32-0.1 mg/kg/injection), and the highest dose of indatraline (0.56 mg/kg/da y) nearly eliminated cocaine-maintained responding. However, doses of indat raline that decreased cocaine self-administration also usually decreased ra tes of food-maintained responding and produced behavioral stereotypies and trends toward weight loss and mild anemia. These findings suggest that alth ough 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.