Dopamine uptake in five structures of the brain: Comparison of rate, sodium dependence and sensitivity to cocaine

Abstract The rate of uptake of dopamine (DA) per μg protein and the sensitivity of uptake to sodium ([Na] o ) and cocaine, have been measured in synaptosomes from five structures in the brain of the rat: striatum, nucleus accumbens, neocortex, limbic cortex and thalamus. Probably reflecting the number of DA terminals, there was a wide variation in the rate of uptake in the different structures: uptake was far greater in the striatum and nucleus accumbens (10–20-fold) than in the neocortex, limbic cortex or thalamus. Uptake in all structures was inhibited by cocaine. With high [Na] o , the IC 50 's varied from 1.10 μM for the thalamus to 3.32 μM for the nucleus accumbens. Maximum percentage inhibition varied from 76.0 for limbic cortex to 96.8 for nucleus accumbens and 97.7 for striatum; thus most uptake was carried-mediated. With low [Na] o , IC 50 for the nucleus accumbens was unchanged, while the IC 50 's for the striatum and limbic cortex were less. Maximum percentage inhibition was similar to that found for high [Na] o . Although the sensitivity to [Na] varied, synaptosomes from all areas showed Na-dependent uptake; lowering [Na] in the incubation medium from 133.2 to 9.5 mM reduced the uptake by a minimum of 36.9% in the neocortex to a maximum of 78.0% in striatum. Neither the rate of uptake nor the Na-dependence correlated precisely with the sensitivity to cocaine but the two structures which showed the greatest rate of uptake (nucleus accumbens and striatum) also showed the greatest sensitivity to [Na] o . Generally, the rate of uptake correlated with the density of DA terminals and number of cocaine binding sites as reported by others. The results are consistent with the conclusion that the nucleus accumbens and striatum are particularly important in the cocaine abuse syndrome because of two factors: (1) the high rate of uptake as a result of the high density of DA terminals predisposes the functions of these structures to a greater impact by cocaine; (2) as a consequence, the overall cocaine abuse syndrome depends to a great extent on the specific functions that these structures subserve.