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 calcium antagonist flunarizine on hippocampal acetylcholine (ACh) release with the 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 concentration of ACh in the hippocampus of rats treated with PTZ alone was significantly reduced relative to that of vehicle-treated 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 expression of PTZ-induced kindling was not prevented by administration of flunarizine. 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 the dopamine D2 antagonist, (-)-sulpiride, suggesting that the decrease in Ca2+ overload by a blockade of the L-type calcium channel may be responsible for the protective action on cholinergic neurons exerted by flunarizine. These data also suggest a potential therapeutic role for flunarizine in counteracting impairment of hippocampal cholinergic activity.
Serra
M
M
Department of Experimental Biology, University of Cagliari, Italy. mserra@vaxca1.unica.it
Dazzi
L
L
Caddeo
M
M
Floris
C
C
Biggio
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors; D003292:Convulsants / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism
D000927:Anticonvulsants; D003292:Convulsants; D000109:Acetylcholine; D005444:Flunarizine; D002118:Calcium; D010433:Pentylenetetrazole