The effects of kindling during pregnancy on long-term potentiation (LTP) induction and M1 muscarinic acetylcholine receptors in male rat offspring

Ali Pourmotabbed , Razieh Naghizadeh, Farshad Moradpour , Mozhgan Veisi, Seyed Ershad Nedaei, Fatemeh Zarei, Zahra Salimi


Background and purpose: Neonates of pregnant women with epilepsy may compromise normal neurodevelopment and hippocampal morphology. Memory and learning disorders and a decrease in verbal IQ scores are seen in these children later in life. In the previous study, we suggested that the central muscarinic cholinergic receptors had an important role in learning and memory deficits induced by prenatal pentylenetetrazol-kindling in pups born to kindled mothers. This study aimed to investigate the effects of kindling during pregnancy on long-term potentiation (LTP) induction and the role of M1 muscarinic acetylcholine receptors in the hippocampus of male offspring.

Experimental approach: Twenty female Wistar rats were divided into two groups on the 13th day of their gestation (kindled and control; n = 10). Animals in the first group were kindled by i.p. injections of 25 mg/kg body weight pentylenetetrazol every 15 min until seizures occurred and the control group received normal saline. The effect of maternal seizures and perfusion of specific M1 muscarinic receptors antagonist (telenzepine at doses of 0.01, 0.1, and 1 nmol) on the LTP induction of 80 pups were tested at 12 weeks of age by field potential recordings.

Findings/Results: The results of the electrophysiological study revealed that recurrent seizures during pregnancy impaired field excitatory postsynaptic potentials (fEPSP)-LTP induction and normal development of M1 muscarinic receptors in the hippocampus of male offspring. Also, the results demonstrated that maternal seizure did not significantly affect the paired-pulse indexes and population spike-LTP in the hippocampus of male offspring.

Conclusion and implications: Our study showed that recurrent seizures during pregnancy cause impaired fEPSP-LTP induction and abnormal development of the M1 muscarinic receptor in the hippocampus.


LTP induction; Maternal seizure; M1 muscarinic acetylcholine receptor; Telenzepine.

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