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

@article{Wee2006ARR,
  title={A Reduced Rate of In Vivo Dopamine Transporter Binding is Associated with Lower Relative Reinforcing Efficacy of Stimulants},
  author={Sunmee Wee and F. Ivy Carroll and William L. Woolverton},
  journal={Neuropsychopharmacology},
  year={2006},
  volume={31},
  pages={351-362}
}
A slow onset of action has been hypothesized to weaken the reinforcing effects of drugs. The present study evaluated this hypothesis with slow-onset cocaine analogs, WIN 35428, RTI 31, and RTI 51. When cocaine or a cocaine analog was made available to rhesus monkeys (n=4 or 5) for self-administration under a progressive-ratio (PR) schedule with a 1-h time-out between injections, all the drugs functioned as positive reinforcers. The maximum number of injections was in the order of cocaine>WIN… 
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Background Citations
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Results Citations
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35 Citations

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Low abuse liability of BZT analogs is supported and their potential development as medications for cocaine abuse is supported by the effects of their oral pretreatment on cocaine self-administration.
Assessment of the effects of contingent histamine injections on the reinforcing effectiveness of cocaine using behavioral economic and progressive-ratio designs
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Results indicate that combining drug punisher with drug reinforcers reduces the maximum reinforcing effect of the drug reinforcer, which suggests a use for drug punishers as a deterrent to drug abuse (e.g., as mixtures with prescription medications with abuse potential).
Self-administration of drug mixtures by monkeys: combining drugs with comparable mechanisms of action
TLDR
Mixtures of various proportions of two drugs with comparable mechanisms of action were additive, i.e., they did not interact, and this result will serve as the basis for comparison to studies of mixtures of drugs with various mechanisms ofaction.
The abuse-related effects of pyrrolidine-containing cathinones are related to their potency and selectivity to inhibit the dopamine transporter
TLDR
These synthetic cathinones were more effective reinforcers than cocaine, and the measures of reinforcing effectiveness determined by PR and demand curve analyses were highly correlated with selectivity for DAT over SERT.
Nonclassical Pharmacology of the Dopamine Transporter: Atypical Inhibitors, Allosteric Modulators, and Partial Substrates
TLDR
Compounds with conformation-specific activity are discussed, useful not only as tools for studying the mechanics of dopamine transport, but also as leads for medication development in addictive disorders.
The Atypical Stimulant and Nootropic Modafinil Interacts with the Dopamine Transporter in a Different Manner than Classical Cocaine-Like Inhibitors
TLDR
Modafinil displayed affinity ratios similar to those of benztropine, GBR12909 and bupropion, but far different than those of cocaine, β-CFT or methylphenidate, and it was demonstrated that the conformational effects of a given DAT inhibitor influence its phenomenological effects.
Interaction of cocaine‐, benztropine‐, and GBR12909‐like compounds with wild‐type and mutant human dopamine transporters: molecular features that differentially determine antagonist‐binding properties
TLDR
This study furthers the concept of using DAT mutants to differentiate cocaine‐like inhibitors from atypical inhibitors in vitro, and points to the importance of specific molecular features – most notably the presence of a diphenylmethoxy moiety – in determining a compound’s binding profile.
Self-administration of cocaine–remifentanil mixtures by monkeys: an isobolographic analysis
TLDR
Combinations of cocaine and remifentanil can be additive or super-additive as positive reinforcers, depending on proportions of each.
Pharmacological determinants of the reinforcing effects of psychostimulants: relation to agonist substitution treatment.
  • J. Lile
  • Psychology, Medicine
    Experimental and clinical psychopharmacology
  • 2006
TLDR
Evidence is presented to support the conclusion that affinity for dopamine transporters appears to be of critical importance, whereas serotonintransporters seem to serve a modulatory function, and that slow-onset, long-acting monoamine transporter ligands can be expected to have reinforcing effects and therefore abuse liability, which has implications for the use of these drugs as pharmacotherapies.
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