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Vol. 280, Issue 2, 541-550, 1997
-Propanoyl-3-(4-Tolyl)-Tropane in Rhesus
Monkeys1
Center for the Neurobiological Investigation of Drug Abuse,
Departments of Physiology and Pharmacology (M.A.N., K.A.G., R.H.M.,
S.R.C.),
Comparative Medicine (M.A.N., K.A.G.) and
Radiology (R.H.M.),
Bowman Gray School of Medicine, Wake Forest University, Winston-Salem,
North Carolina and
Department of Chemistry (H.M.L.D.), Wake Forest
University, Winston-Salem, North Carolina
2
-propanoyl-3-(4-tolyl)-tropane (PTT), is a cocaine analog that
inhibits dopamine uptake, binding with high affinity and selectivity to
the dopamine transporter. In the present study, the behavioral effects
of PTT were evaluated in two models of cocaine abuse: drug
self-administration and drug discrimination. In the first experiment,
rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a
fixed-interval 5-min schedule. Presession administration of PTT
(0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self-administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to
1.0 log units more potent than cocaine. In experiment 2, the
reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were evaluated
in a separate group of monkeys (n = 4) responding
under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than
rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session
PTT intake was significantly lower than cocaine intake. In experiment
3, the discriminative stimulus effects of PTT (0.003-0.1 mg/kg, i.m.)
were evaluated in monkeys (n = 3) trained to
discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT
substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose,
cocaine-appropriate responding was observed 8 to 24 hr after the
injection. These results demonstrated that the long-acting indirect
dopamine agonist PTT was effective in decreasing cocaine
self-administration and in abuse liability testing showed a unique
behavioral profile, not functioning as a reinforcer when substituted
for cocaine and producing discriminative stimulus effects similar to
cocaine.
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