Effect of pirenzepine, a muscarinic M-1 receptor antagonist, on amygdala kindling in rat

Kindling, an animal model of complex partial seizures with secondary genera lization, is performed by daily application of low-intensity electrical bra in stimulation. The purpose of this study was to investigate the role of mu scarinic M-1 receptors on amygdala kindling in the rat. Bipolar nichrome st imulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were a lso placed bilaterally in the skull over the cortex. Amygdala stimulation w as applied twice daily at the current intensity of afterdischarge threshold . Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 1 00 nmol), a muscarinic M-1 receptor antagonist, was injected intracerebrove ntricularly 1 h before the electrical stimulation. In the second group of e xperiments, rats were kindled to full stage 5 seizures. After a recovery pe riod, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pre treated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development an d increased the total number of stimulations required to reach the first st age 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected b y pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M-1 receptors may have a critical role in the development o f kindling epileptic activity, but not in already kindled seizures. (C) 199 9 Elsevier Science B.V. All rights reserved.