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

Eur J Pharmacol. 1999 Feb 19;367(2-3):175-81. doi: 10.1016/s0014-2999(98)00967-4.


Local anesthetics bind to dopamine transporters and inhibit dopamine uptake in rodent brain. Additionally, local anesthetics are self-administered in rhesus monkeys. The present study determined binding affinities of cocaine and five local anesthetics at dopamine transporters in rhesus monkey brain, and compared binding affinities to published self-administration potencies in rhesus monkeys. The affinity order at dopamine transporters was cocaine > dimethocaine > tetracaine > procaine > or = chloroprocaine > lidocaine. The correlation between dopamine transporter affinities and self-administration potencies was significant. Binding affinities were also determined at sodium (Na2+) channels in rhesus monkey brain. There was not a significant correlation between Na2+ channel affinities and self-administration potencies Local anesthetics with high dopamine transporter and low Na2+ channel affinities were self-administered, whereas those with either high or low affinity at both sites were not consistently self-administered. These data suggest that affinity at dopamine transporters is related to the reinforcing effects of local anesthetics in rhesus monkeys, and Na2+ channel effects may interfere with the reinforcing effect of these drugs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / metabolism*
  • Animals
  • Brain / physiology*
  • Carrier Proteins / metabolism*
  • Caudate Nucleus / physiology
  • Cocaine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Drug Synergism
  • Frontal Lobe / physiology
  • In Vitro Techniques
  • Macaca mulatta
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Protein Binding
  • Putamen / physiology
  • Self Medication*
  • Sodium Channels / metabolism


  • Anesthetics, Local
  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Sodium Channels
  • Cocaine