The Reinforcing Efficacy of the Dopamine Reuptake Inhibitor 2β-Propanoyl-3β-(4-tolyl)-tropane (PTT) as Measured by a Progressive-Ratio Schedule and a Choice Procedure in Rhesus Monkeys

@article{Lile2002TheRE,
  title={The Reinforcing Efficacy of the Dopamine Reuptake Inhibitor 2$\beta$-Propanoyl-3$\beta$-(4-tolyl)-tropane (PTT) as Measured by a Progressive-Ratio Schedule and a Choice Procedure in Rhesus Monkeys},
  author={Joshua A Lile and Drake Morgan and Anne M. Birmingham and Zhixia Wang and William L. Woolverton and Huw M. L. Davies and Michael A. Nader},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2002},
  volume={303},
  pages={640 - 648}
}
  • J. Lile, D. Morgan, M. Nader
  • Published 1 November 2002
  • Biology, Psychology
  • Journal of Pharmacology and Experimental Therapeutics
The present series of experiments was undertaken to investigate the variables that influence the reinforcing efficacy of psychostimulants. The time of onset for dopamine transporter (DAT) occupancy of the long-acting, high-affinity DAT blocker 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) was measured using an ex vivo binding assay in rodents and was determined to be significantly longer than for cocaine (30 min versus 2 min). To assess the reinforcing efficacy of PTT relative to cocaine, a discrete… 

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References

SHOWING 1-10 OF 42 REFERENCES

Further evaluation of the reinforcing effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane (PTT) in rhesus monkeys

TLDR
It is suggested that for long-acting compounds like PTT, reinforcing effects are more likely to be observed when the drug is available under a ratio-based schedule, compared to an interval- based schedule.

The reinforcing and discriminative stimulus effects of the novel cocaine analog 2beta-propanoyl-3beta-(4-tolyl)-tropane in rhesus monkeys.

TLDR
It is 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.

Self-administration of two long-acting monoamine transport blockers in rhesus monkeys

TLDR
The results indicate that the reinforcing effects of PTT were slightly modified by a brief history of cocaine reinforcement, and that the weak reinforcing effects were most apparent when the drug was available under unlimited-access conditions.

Comparison of a novel tropane analog of cocaine, 2 beta-propanoyl-3 beta-(4-tolyl) tropane with cocaine HCl in rats: nucleus accumbens extracellular dopamine concentration and motor activity.

TLDR
Comparing the quantitative and temporal effects of PTT and cocaine on in vivo neurochemical measures and motor behavior shows similar in vivo potencies for PTT on nucleus accumbens [DA]e and locomotor activity, however, these data do not support the hypothesis that the time course of increased nucleus accumens [ DA]E and stimulated locomotorActivity are related.

Behavioral and local cerebral metabolic effects of the novel tropane analog, 2 beta-propanoyl-3 beta-(4-tolyl)-tropane.

TLDR
The present data demonstrate that PTT acts as a stimulant in vivo, paralleling its effects in vitro, but its behavioral and cerebral metabolic effects are qualitatively different from those of cocaine.

Self-administration of the high-affinity cocaine analog 2β-carbomethoxy-3β-(4-fluorophenyl)tropane

Reinforcing and discriminative stimulus effects of β-CIT in rhesus monkeys

Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys.

TLDR
The results in conjunction with those of previous studies in squirrel monkeys reveal a close correspondence between the relative potencies of cocaine and related drugs for maintaining i.v. self-administration and for increasing rates of schedule-controlled responding, suggesting that the reinforcing and psychomotor-stimulant effects of the drugs are mediated similarly.

Self-administration of cocaine analogs by rats

TLDR
The data suggest that drugs with a higher affinity for the DA versus the 5-HT transporter are more likely to be self-administered than those with a lower affinity.

Evaluation of the role of norepinephrine in the reinforcing effects of psychomotor stimulants in rhesus monkeys

  • W. Woolverton
  • Biology, Psychology
    Pharmacology Biochemistry and Behavior
  • 1987