TRANSPORT OF DOPAMINE AT THE BLOOD-BRAIN-BARRIER OF THE GUINEA-PIG - INHIBITION BY PSYCHOTROPIC-DRUGS AND NICOTINE

Purpose. Transport of dopamine (DA) across the blood-brain barrier (BB B) was examined in guinea pigs. Methods, In situ brain perfusion (1-10 min), capillary depletion, and high pressure liquid chromatography (H PLC) were used. Results, There was a saturable DA influx into the brai n with a K-M of 389 +/- 55 nM, and a V-MAX of 1.95 +/- 0.25 pmol/min/g of brain. The diffusion constant, K-D, was not significantly differen t from zero. About 0.5% of DA remained tightly bound to cerebral micro vessels isolated from the perfused brain. DA influx into the brain was not altered by the monoamine oxidase-B (MAO-B) inhibitor pargyline (5 0 mu M) HPLC analysis of perfused brain confirmed transport of intact DA, and no detectable increases in DA metabolites were observed. At pe rfusate concentrations of 500 nM, several dopaminergic receptor antago nists inhibited [H-3]-DA (21 nM) influx; the percent inhibitions for t he mixed D, and Dt antagonists haloperidol and chlorpromazine, the D-1 antagonist SCH-23390, and the D-2 antagonist spiperone were 90%, 68%, 77%, and 50%, respectively Brain perfusion with nicotine (500 nM) inh ibited DA uptake by 86%. This nicotine effect was not altered by mecam ylamine, but was partially prevented by the nicotinic receptor antagon ist hexamethonium. Conclusions. a) A significant cerebrovascular perme ability to intact DA is mediated by a MAO-B independent specific trans port system at the BBB, b) this system could be inhibited by D-1 and D -2 DA receptor antagonists, and c) DA blood-to-brain transport was inh ibited by nicotine.