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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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.
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Combinations of cocaine and remifentanil can be additive or super-additive as positive reinforcers, depending on proportions of each.
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  • 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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