Effects of 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) on the self-administration of cocaine, heroin, and cocaine/heroin combinations in rats.
Pharmacotherapies utilizing long-acting agonists and mixed function agonists-antagonists have been successful in the treatment of opiate addiction but no comparable treatment exists for cocaine abuse. Long-acting tropane analogues have been synthesized that could be candidates for such pharmacotherapies. 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) is one such compound that is a relatively selective dopamine (DA) transporter blocker that has a significantly longer duration of action than cocaine. The purpose of this study was to assess the effects of PTT on the intravenous self-administration of cocaine, heroin, or cocaine/heroin combinations. Groups of rats were trained to self-administer cocaine, heroin, or cocaine/heroin combinations using a within session dosing procedure in which three doses were available each session. PTT pretreatment reduced cocaine and cocaine/heroin combinations intake in a dose-dependent manner while having only minor effects on heroin intake. These results suggest that the neurobiological substrates of cocaine and heroin self-administration are different, and that these cocaine/heroin combinations may function more like cocaine alone, even when the dose of heroin in the mixture will function independently as a reinforcer. These results further support the potential use of long-acting dopamine reuptake inhibitors as pharmacotherapeutic adjuncts to a comprehensive treatment program for cocaine and cocaine/heroin abuse.
Sizemore
Glen M
GM
Department of Psychology, University of Florida, Box 112250, Gainesville, FL 32611, USA.
Davies
Huw M L
HM
Martin
T J
TJ
Smith
James E
JE
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003932:Heroin / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012054:Reinforcement, Psychology; D012646:Self Administration; D019966:Substance-Related Disorders / Q000188:drug therapy*
D018765:Dopamine Uptake Inhibitors; C087634:2-propanoyl-3-(4-tolyl)tropane; D003932:Heroin; D003042:Cocaine