The effect of rivastigmine on spike wave discharges in WAG/Rij rats with genetic absence epilepsy

Introduction-Aim: The present study, we aimed to investigate the effects of Rivastigmine (RIVA), an acetylcholinesterase inhibitor used in the treatment of dementia symptoms, with/without the T-type calsium channel blocker NNC 55-0396 (NNC) on spike-wave discharges (SWDs); comorbidities (learning-memory and anxiety) and and the TRPV1 geneexpression in genetic absence epileptic WAG/Rij rats. Methods: To determine the effect of RIVA on SWDs, tripolar electrodes were placed on the skulls of WAG/Rij rats then acute and long-term recordings were obtained. After this stage, the interaction between RIVA and T-type calcium channel blocker NNC 55-0396 (NNC) was studied. Learning-memory and anxiety behavior tests were performed to WAG/Rij and Wistar rats that given long-term (21 days) effective dose of RIVA. Right somatosensory cortex and hippocampus of rats extracted for determining the TRPV1 gene expression by qPCR after behavioral tests. Results: Acute RIVA administrations at the doses of 0.25; 0.5; 1 and 2 mg/kg decreased the number of SWDs in a dose-dependent manner. Only 1 and 2 mg/kg RIVA had a decreasing effect regarding the mean duration per SWDs. The combination of ineffective dose of RIVA (0.125 mg/kg; intraperitoneal (i.p.)) and ineffective dose of NNC (5 µgr; i.s.v.) also decreased the total number of SWDs. When the effective dose of RIVA (2 mg/kg) was long-term administered, it increased the number of SWDs and decreased the mean duration. Long-term high-dose RIVA that applied to WAG/Rij rats negatively affected short-term memory, while reduced anxiety. Based on qPCR results, TRPV1 gene expressions were decreased in WAG/Rij rats, although it was increased in Wistar strain. Conclusions: While RIVA has an antiepileptic effect administered acutely, RIVA produces proepileptic activity when applied for a long-term. We suggest that the antiepileptic effect of acute RIVA may be mediated through T-type calcium channel inhibition. RIVA administration negatively affected learning-memory, while reduced anxiety. On the other hand, when long-term RIVA was administered to WAG/Rij and Wistar rats, contradictory results were obtained regarding TRPV1 expressions.