The role of acetylcholinesterase enzyme inhibitor rivastigmine on spike-wave discharges, learning-memory, anxiety, and TRPV1 channel expression in genetic absence epileptic WAG/Rij rats

Abstract In the present study, the effects of the acetylcholinesterase (AChE) enzyme inhibitor rivastigmine (RIVA) on spike-wave discharges (SWDs), memory impairment, anxiety-like behavior, and TRPV1 gene expression were investigated in genetic absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. After tripolar electrodes were implanted on the WAG/Rij rats' skulls, single doses of 0.125, 0.25, 0.5, 1, 2 mg/kg RIVA was intraperitoneally (i.p.) administered and electrocorticogram (ECoG) recordings of SWDs were obtained for three hours before and after injections. Additionally, WAG/Rij rats were administered low-dose (0.5 mg/kg) and high-dose (2 mg/kg) of RIVA for consecutive 21 days and SWDs were recorded. Learning-memory abilities (Y-maze test), anxiety-like behavior (elevated plus maze test), and TRPV1 gene expression were determined and compared in 8-month-old WAG/Rij and age-matched Wistar rats. Acute RIVA administration dose-dependently reduced the total number and mean duration of SWDs, even entirely inhibited at the doses of 1 and 2 mg/kg RIVA. Whereas long-term high-dose administration of RIVA increased the total number of SWDs, however, decreased the mean duration. Long-term high-dose RIVA treatment reduced learning-memory and anxiety-like behavior in WAG/Rij rats, while only anxiety-like behavior decreased in Wistar rats. According to the qPCR analysis, long-term RIVA administration reduced the TRPV1 gene expression in WAG/Rij rats, in fact, TRPV1 increased in Wistar rats. These data indicate that single-dose RIVA administration dose-dependently decreases absence seizures, however, long-term administration of RIVA increases absence seizures probably by altering channel expressions such as TRPV1.