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Effects of 2beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) on the self-administration of cocaine, heroin, and cocaine/heroin combinations in rats.

Abstract
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.
AuthorsGlen M Sizemore, Huw M L Davies, T J Martin, James E Smith
JournalDrug and alcohol dependence (Drug Alcohol Depend) Vol. 73 Issue 3 Pg. 259-65 (Mar 08 2004) ISSN: 0376-8716 [Print] Ireland
PMID15036548 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Dopamine Uptake Inhibitors
  • 2-propanoyl-3-(4-tolyl)tropane
  • Heroin
  • Cocaine
Topics
  • Analysis of Variance
  • Animals
  • Cocaine (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
  • Dopamine Uptake Inhibitors (pharmacology, therapeutic use)
  • Heroin (administration & dosage)
  • Male
  • Rats
  • Rats, Inbred F344
  • Reinforcement, Psychology
  • Self Administration
  • Substance-Related Disorders (drug therapy)

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