PT - JOURNAL ARTICLE AU - S. Stevens Negus AU - Michael R. Brandt AU - Nancy K. Mello TI - Effects of the Long-Acting Monoamine Reuptake Inhibitor Indatraline on Cocaine Self-Administration in Rhesus Monkeys DP - 1999 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 60--69 VI - 291 IP - 1 4099 - http://jpet.aspetjournals.org/content/291/1/60.short 4100 - http://jpet.aspetjournals.org/content/291/1/60.full SO - J Pharmacol Exp Ther1999 Oct 01; 291 AB - 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. The American Society for Pharmacology and Experimental Therapeutics