Relationship between injection duration, transporter occupancy and reinforcing strength of cocaine.
Among drugs that can function as positive reinforcers, slower occupancy of central nervous system sites of action has been associated with diminished reinforcing strength. The present study examined the relative reinforcing strength of cocaine, and the rate of in vivo dopamine transporter binding, as a function of injection duration. Rhesus monkeys (N=5) were allowed to self-administer cocaine under a progressive-ratio schedule with doses injected over different times (10-600 s). An ex vivo dopamine transporter binding assay was used to examine kinetics of in vivo transporter occupancy by cocaine injected over the same times in rats. Cocaine was a weaker reinforcer, and dopamine transporter binding rate decreased, with slower injections. Maximum transporter binding was the same across injection durations. These results support the hypothesis that slower onset of action is associated with a slower transporter occupancy and diminished reinforcing strength. Relative strength as a reinforcer may not be determined by maximum occupancy, at least not exclusively.
Woolverton
William L
WL
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Guyton Research Building, 2500 North State Street, Jackson, MS 39216-4505, USA. Wwoolverton@psychiatry.umsmed.edu
Wang
Zhixia
Z
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine; D004298:Dopamine