Reversal by flunarizine of the decrease in hippocampal acetylcholine release in pentylenetetrazole-kindled rats

The aim of our study was to evaluate the effect of the non-selective calciu m antagonist flunarizine on hippocampal acetylcholine (ACh) release with th e microdialysis technique in freely moving rats after long-term concomitant administration of pentylenetetrazole (PTZ) in comparison with rats treated long-term with PTZ (kindled animals). The basal extracellular concentratio n of ACh in the hippocampus of rats treated with PTZ alone was significantl y reduced relative to that of vehicle-created rats (2.04 +/- 0.2 vs 3.94 +/ - 0.3 pmol per 20-min sample; P < 0.01) Administration of flunarizine (7.5 mg/kg i.p.) before each PTZ injection prevented this decrease in basal ACh output (3.75 +/- 0.4 pmol per 20 min sample). On the contrary, the expressi on of PTZ-induced kindling was not prevented by administration of flunarizi ne. The specific antagonistic effect of flunarizine on the kindling-induced decrease in hippocampal ACh release is shared by the selective antagonist of the L-type calcium channel, nifedipine, but not by die dopamine D-2 anta gonist, (-)-sulpiride, suggesting that the decrease in Ca2+ overload by a b lockade of the L-type calcium channel may be responsible for the protective action on cholinergic neurons exerted by flunarizine. These data also sugg est a potential therapeutic role for flunarizine in counteracting impairmen t of hippocampal cholinergic activity. BIOCHEM PHARMACOL 58;1:145-149, 1999 . (C) 1999 Elsevier Science Inc.