DOPAMINE UPTAKE IN 5 STRUCTURES OF THE BRAIN - COMPARISON OF RATE, SODIUM DEPENDENCE AND SENSITIVITY TO COCAINE

The rate of uptake of dopamine (DA) per mug protein and the sensitivit y of uptake to sodium ([Na]o) and cocaine, have been measured in synap tosomes from five structures in the brain of the rat: striatum, nucleu s accumbens, neocortex, limbic cortex and thalamus. Probably reflectin g the number of DA terminals, there was a wide variation in the rate o f uptake in the different structures: uptake was far greater in the st riatum and nucleus accumbens (10-20-fold) than in the neocortex, limbi c cortex or thalamus. Uptake in all structures was inhibited by cocain e. With high [Na]o, the IC50's varied from 1.10 muM for the thalamus t o 3.32 muM for the nucleus accumbens. Maximum percentage inhibition va ried from 76.0 for limbic cortex to 96.8 for nucleus accumbens and 97. 7 for striatum; thus most uptake was carrier-mediated. With low [Na]o, IC50 for the nucleus accumbens was unchanged, while the IC50's for th e 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; l owering [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% i n striatum. Neither the rate of uptake nor the Na-dependence correlate d precisely with the sensitivity to cocaine but the two structures whi ch 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 coca ine binding sites as reported by others. The results are consistent wi th the conclusion that the nucleus accumbens and striatum are particul arly 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 termi nals 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 structu res subserve.