Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey

The behavioral effects of 3 beta-(4-chlorophenyl)tropane-2 beta-carboxylic acid phenyl ester hydrochloride (RTI-113; 0.03-1.0 mg/ kg), a selective dop amine uptake inhibitor, were compared with those of cocaine (0.03-3.0 mg/kg ) and 1-{2-[bis(4-fluorophenyl) methoxy]ethyl}-4-(3-phenylpropyl)piperazine dihydrochloride (GBR 12909; 0.03-3.0 mg/ kg) in squirrel monkeys. Intermed iate doses of each drug produced significant increases in response rate mai ntained by a fixed-interval (FI) 300-s schedule of stimulus termination, bu t RTI-113 was less effective than cocaine or GBR 12909. The order of potenc y for increasing response rate was RTI-113 greater than or equal to cocaine . GBR 12909. In drug time course determinations, RTI-113 and GBR 12909 had longer durations of action than cocaine. RTI-113 substituted completely for cocaine in subjects trained to discriminate cocaine and saline under a two -lever drug-discrimination procedure maintained by food delivery. RTI-113 a lso reliably maintained self-administration behavior in subjects trained un der a second-order FI 900-s schedule of i.v. cocaine delivery. Pretreatment with RTI-113 significantly decreased responding for cocaine at the highest pretreatment dose, but RTI-113 had similar effects on responding maintaine d by a second-order FI 900-s schedule of stimulus termination. The results indicate that the behavioral pharmacology of RTI-113 is similar to that of cocaine, further implicating a prominent role for dopamine uptake inhibitio n in the behavioral effects of cocaine. Its longer duration of action in co njunction with less pronounced behavioral-stimulant effects are desirable p roperties for a substitute pharmacotherapy for cocaine abuse. RTI-113 effec tively decreased cocaine self-administration behavior, although its direct rate-altering effects may have contributed to the interactions obtained.