Plastic Changes and Disease-modifying Effects of Scopolamine in the Pilocarpine Model of Epilepsy in Rats

Summary:  Purpose: We describe the use of a clinically relevant pharmacological intervention that alters the clinical history of status epilepticus (SE)-induced spontaneous recurrent seizures (SRS) in the pilocarpine model and the possible plastic changes underlying such an effect.
Methods: Two hours after pilocarpine-induced SE (320–350 mg/kg, i.p.), rats received scopolamine 1–2 mg/kg i.p. or saline, every 6 h for 3 days. After that, osmotic minipumps were implanted for continuous delivery of scopolamine or saline for an additional 14 days. Animals were video-monitored for 12 h/week during the following 3-month period for the occurrence of SRS and, thereafter, were perfused, processed, and coronal brain sections were stained for acetylcholinesterase (AChE) and for the presence of supragranular mossy fibers (Timm).
Results: Treatment with scopolamine led to significantly fewer SRS. Staining for AChE in the dentate gyrus was significantly more intense in naïve animals. The scopolamine group had the least intense AChE staining of all groups. However, regression analysis of the AChE staining for this group did not correlate with the presence or absence of SRS, or the latency or frequency of SRS. Supragranular mossy fiber sprouting developed in all animals experiencing pilocarpine-induced SE, irrespective of whether or not they were treated with scopolamine.
Conclusions: Pilocarpine-induced SE in the presence of scopolamine might produce animals that, despite mossy fiber sprouting, were not seen to exhibit spontaneous seizures. In addition, our data suggest that the encountered changes in the AChE staining in the dentate gyrus that followed treatment with scopolamine do not help to explain its disease-modifying effects.