On the relationship between the dopamine transporter and the reinforcing effects of local anesthetics in rhesus monkeys: practical and theoretical concerns

  title={On the relationship between the dopamine transporter and the reinforcing effects of local anesthetics in rhesus monkeys: practical and theoretical concerns},
  author={Kristin M. Wilcox and James K. Rowlett and Ian A. Paul and Gregory A. Ordway and William L. Woolverton},
Abstract.Rationale: Drugs that are self-administered appear to vary in their potency and effectiveness as positive reinforcers. Understanding mechanisms that determine relative effectiveness of drugs as reinforcers will enhance our understanding of drug abuse. Objectives: The hypothesis of the present study was that differences among dopamine transporter (DAT) ligands in potency and effectiveness as a positive reinforcers were related to potency and effectiveness as DA uptake inhibitors… 

In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys

Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques, and further support a role for the DAT in the abuse liability of local anesthetics.

Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys

Reinforcing Strength of a Novel Dopamine Transporter Ligand: Pharmacodynamic and Pharmacokinetic Mechanisms

The results suggest that (+)-CPCA is a weaker positive reinforcer than cocaine because it has a slower onset of action over the first few minutes after i.v. injection.

Reinforcing and discriminative stimulus effects of RTI 111, a 3-phenyltropane analog, in rhesus monkeys: interaction with methamphetamine

The data suggest that RTI 111 is behaviorally similar to traditional psychomotor stimulants that act at the DA transporter and that it increases, rather than blocks, the behavioral potency of MA.

A Reduced Rate of In Vivo Dopamine Transporter Binding is Associated with Lower Relative Reinforcing Efficacy of Stimulants

The hypothesis that a slow onset at the DAT is associated with reduced reinforcing efficacy of DAT ligands is supported and RTI 31 was shown to function as a positive reinforcer in drug-naïve rhesus monkeys under a fixed-ratio 1 schedule.

Self-administration of cocaine: scopolamine combinations by rhesus monkeys

This study supports the hypothesis that anticholinergic actions contribute to the diminished self-administration of BZT analogs relative to cocaine.

Simultaneous measurement of extracellular dopamine and dopamine transporter occupancy by cocaine analogs in squirrel monkeys

The results suggest a lack of concordance between drug occupancy at DAT and changes in DA levels, and indicate that acute cocaine administration decreases the availability of plasma membrane DAT for binding, even after cocaine is no longer blocking DA uptake as evidence by a return to basal DA levels.



The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys.

Why some, but not all, D1 receptor agonists can function as reinforcers in rhesus monkeys is examined by comparing behavioral and CNS in vitro measures of potency and efficacy, and reinforcing efficacy among D1 agonists increases with efficacy in stimulating D1 receptors.

Comparison between dopamine transporter affinity and self-administration potency of local anesthetics in rhesus monkeys.

Self-administration of cocaine analogs by rats

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.

3’- and 4’-chloro-substituted analogs of benztropine: intravenous self-administration and in vitro radioligand binding studies in rhesus monkeys

Abstract Rationale: The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission. Drugs that block dopamine (DA) uptake have generally been

Behavioral pharmacology of local anesthetics: Reinforcing and discriminative stimulus effects

Relationship between psychostimulant-induced "high" and dopamine transporter occupancy.

  • N. VolkowG. Wang J. Lieberman
  • Psychology, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1996
It is indicated that DAT occupancy is not sufficient to account for the high, and that for DAT inhibitors to be therapeutically effective, occupancies > 80% may be required.

In vitro and in vivo effects of cocaine and selected local anesthetics on the dopamine transporter.

Comparison of the reinforcing properties of cocaine and procaine in rhesus monkeys

Reinforcing properties of some local anesthetics in rhesus monkeys