Ll. Howell et al., Comparative behavioral pharmacology of cocaine and the selective dopamine uptake inhibitor RTI-113 in the squirrel monkey, J PHARM EXP, 292(2), 2000, pp. 521-529
Citations number
49
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
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.