Presynaptic L-type Ca2+ channels on excessive dopamine release from rat caudate putamen

We investigated by means of behavioral and neurochemical studies the role o f the nerve terminal L-type voltage sensitive Ca2+ channel on dopamine (DA) release. Microinjection of Bay K 8644 (BAYK), an L-type Ca2+ channel stimu lant, into the rat caudate putamen increased locomotor activity and rearing behavior in a dose-dependent manner, whereas injections into the amygdala had no effect. DA receptor antagonists significantly blocked BAYK-induced h yperactivity. Significant increases of extracellular DA levels were detecte d by microdialysis 20 min after BAYK administration into caudate putamen an d then declined. This increase was influenced by tetrodotoxin, an axonal Na + channel blocker. Pretreatment with nimodipine and nicardipine, but not ni fedipine, which are 1.4-dihydropyridine L-type Ca2+ channel antagonists, ad ministered into the caudate putamen significantly blocked BAYK-induced hype ractivity and DA efflux. These results indicate that the extraordinary DA r elease in the caudate putamen was mediated by extreme stimulation of the ni cardipine and nimodipine-sensitive L-type Ca2+ channel present in the nerve terminal of striatal DA neurons. (C) 2000 Elsevier Science Inc. All rights reserved.