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Vol. 291, Issue 1, 60-69, October 1999
Alcohol and Drug Abuse Research Center, Harvard Medical
School-McLean Hospital, Belmont, Massachusetts
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.
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