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

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 greater than or equal to chloroproc aine > lidocaine. The correlation between dopamine transporter affinities a nd self-administration potencies was significant. Binding affinities were a lso determined at sodium (Na2+) channels in rhesus monkey brain. There was not a significant correlation between Na2+ channel affinities and self-admi nistration potencies Local anesthetics with high dopamine transporter and l ow Na2+ channel affinities were self-administered, whereas those with eithe r high or low affinity at both sites were not consistently self-administere d. These data suggest that affinity at dopamine transporters is related to the reinforcing effects of local anesthetics in rhesus monkeys, and Na2+ ch annel effects may interfere with the reinforcing effect of these drugs. (C) 1999 Elsevier Science B.V. All rights reserved.