Antimuscarinic-induced convulsions in fasted mice after food intake: no evidence of spontaneous seizures, behavioral changes or neuronal damage

Nurhan Enginar,Zeynep Güneş Özünal,Gül İpek Gündoğan,Asiye Nurten,Aslı Zengin Türkmen

doi:10.21307/ane-2017-069

Abstract

Prolonged or repeated seizures have been shown to cause spontaneous recurrent seizures, increased anxiety‑related behavior, locomotor hyperactivity, impaired functions of learning and memory, and neuronal damage in the hippocampus and other brain regions in animals. Mice and rats treated with antimuscarinic drugs after fasting for twodays or less develop convulsions after being allowed to eat ad libitum. To address whether such behavioral and neuroanatomic changes occur following these convulsions, mice treated i.p. with saline (control) or 2.4mg/kg atropine and given food after 24 h of fasting were grouped according to seizure scores for behavioral and histological analysis. Following convulsions, the occurrence of spontaneous recurrent seizures was observed for 30days. Motor activity and grooming behavior were assessed in the open field, and memory was assessed using the novel object recognition test 4 and 7days after onset of convulsions, respectively. Animals allocated for the histological analysis were decapitated 7days after onset of convulsions and hippocampal slices were evaluated for the percentage of degenerating neurons stained with Fluoro‑Jade C. Spontaneous recurrent seizures, locomotor alterations, anxiety‑related behavior, memory impairment, and neuronal loss in the granular layer of the dentate gyrus were not detected in the animals with seizure score 1-2 or 3-5. These results are in accordance with those related to the absence of behavioral changes, cognitive deficits, and hippocampal neuronal damage after single brief seizures in animals and patients with epilepsy.

Highlights

In a series of studies, we have shown that mice and rats treated with scopolamine, atropine or biperiden after fasting for two days or less develop convulsions soon after being allowed to eat ad libitum (Nurten and Enginar 2006, Enginar and Nurten 2010)
In view of the facts mentioned above, the present study evaluated whether spontaneous recurrent sei‐ zures, behavioral and cognitive alterations, and his‐ tological changes in the hippocampus occur following convulsions induced by antimuscarinic treatment and food intake in mice fasted for 24 h
The present results showed that mice with seizure score 3–5, as well as, 1–2 displayed no differences from the control group by the recognition index calculated for each animal using the time spent exploring the familiar or novel object (Arque et al 2008, Zhang et al 2012)

Summary

Introduction

In a series of studies, we have shown that mice and rats treated with scopolamine, atropine or biperiden after fasting for two days or less develop convulsions soon after being allowed to eat ad libitum (Nurten and Enginar 2006, Enginar and Nurten 2010). But not its hypoglycemic consequence, seems to be critical in the development of seizures because glucose intake during fasting increases plasma levels almost to fed levels, but could not produce any preventive effect (Enginar et al 2005). Development of convulsions only after solid food intake, but not slurry or fluid feeding, suggests that all of the complicated acts that occur during eat‐ ing (e.g. chewing and swallowing movements, smell‐ ing and tasting), and stimulation of the amygdala by repetitive oral and masticator movements are the triggering and underlying factors (Nurten et al 2009). Bearing some similarities in triggering factors and manifestations of seizures in patients with eating epilepsy, convulsions in fasted animals may provide insight into the mechanism of this rare and partially controlled form of reflex epilepsy (Senanayake 1994, Striano et al 2012)

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