Effects of the Ca2+ channel antagonist flunarizine on visual discrimination learning.

Recent studies report that the peripheral administration of Ca2+ channel antagonists improves memory while central administration impairs memory in neurologically intact subjects. This study compares the effects of systemic versus central administration of the Ca2+ channel antagonist flunarizine on visual discrimination learning. In Experiment 1, 60 five-day-old male chicks received an intraperitoneal injection of 0, 1, 10, or 25 mg/kg flunarizine. Each chick then received three post-treatment test sessions (+5 min, +30 min, and +24 h) consisting of 60 visual discrimination trials followed by 5 min of observation in an open field. Flunarizine produced a dose- and time-dependent facilitation of learning. Evaluation of open-field behaviors indicated that the dose of flunarizine required to increase spontaneous activity was 10 times higher than the dose required to facilitate visual discrimination learning. No other open-field behaviors were effected. In Experiment 2, 44 chicks received intracerbroventricular injections of 0, 100 nM, 100 micro M, or 1 mM flunarizine followed by visual discrimination training as described in Experiment 1. Ventricular injection of flunarizine significantly increased the number of errors made during acquisition and retention trials. These data are consistent with earlier studies showing that systemic, but not central, administration of Ca2+ channel antagonists facilitates learning.