Lamotrigine ameliorates seizures and psychiatric comorbidity in a rat model of spontaneous absence epilepsy

Abstract

SUMMARYPurpose: Lamotrigine (LTG) is an effective clinical treatment for epilepsy associated with absence seizures. However, the impact of LTG administration in studies employing various animal models of epilepsy remains controversial. This study aimed to clarify the outcomes of LTG treatment on absence seizures and comorbid anxiety and depression disorders in Long-Evans rats with spontaneous spike-wave discharges (SWDs). Methods: LTG (10 mg/kg) or water vehicle was chronically administered perorally to Long-Evans rats (twice daily for 35 days). Cortical activities were recorded to assess the presence of SWDs. Five behavioral tests, including the open field (OF), elevated plus maze (EPM), sucrose consumption (SC), sucrose preference, and forced swimming (FS) tests, were performed after LTG/ vehicle treatment. The behavioral indexes of these tests were designed to assess anxiety (OF and EPM tests), depression (SC and FS tests), and preference for hedonistic stimuli (sugar preference test). Key Findings: Total SWD duration, SWD number, and mean SWD duration were significantly decreased in rats that received 35-day LTG treatment compared with rats that received vehicle treatment. Rats with spontaneous SWDs versus rats with no SWDs showed significant levels of anxiety and depression in the OF, EPM, and SC tests. Rats with SWDs also showed longer immobility in the FS test. However, the LTG-treated group compared with the vehicle group presented with significantly lower manifestations of anxiety and depression in the OF, EPM, SC, and sucrose preference tests and shorter immobility in the FS test. Significance: The results of this study suggest that chronic LTG treatment can benefit patients with epilepsy via suppression of absence seizures and amelioration of comorbid anxiety and depression.

Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

“…It is interesting to note that not only WAG/Rij rats and GAERS rats but also Long Evans rats produce SWDs: spontaneous high-voltage rhythmic spike (HVRS) discharges of Long Evans rats in EEG recordings may be considered as SWDs as was demonstrated by analysis of pharmacological, behavioral and EEG features of HVRS activity (Depaulis and Van Luijtelaar, 2005;Huang et al, 2012;Polack and Charpier, 2006;Shaw, 2004Shaw, , 2007Shaw et al, 2009;Van Luijtelaar et al, 2011). However, additional studies (e.g., pharmacological and electrophysiological) are needed to investigate the similarities/differences in the features of absence epileptic activity between WAG/Rij rats, GAERS rats and Long Evans rats in order to include the Long Evans rat strain in the widely accepted models of human absence epilepsy.…”

“…However, additional studies (e.g., pharmacological and electrophysiological) are needed to investigate the similarities/differences in the features of absence epileptic activity between WAG/Rij rats, GAERS rats and Long Evans rats in order to include the Long Evans rat strain in the widely accepted models of human absence epilepsy. According to literature, Long Evans rats may be considered as a model animal of absence epilepsy only to some extent at the moment (Depaulis and Van Luijtelaar, 2005;Huang et al, 2012;Kovács et al, 2013;Polack and Charpier, 2006;Shaw, 2004Shaw, , 2007Shaw et al, 2009;Van Luijtelaar et al, 2011). A typical SWD contains train of spikes and slow waves starting and ending with spikes in all absence epileptic rats, but some differences in features of SWDs in GAERS rats, WAG/Rij rats and Long Evans rats have been revealed.…”

“…However, the effects of LPS on absence epileptic activity in freely moving animals have not been investigated in genetically epileptic GAERS rats and Long Evans rats. It was recently demonstrated that Long Evans rats also produce SWDs similarly to WAG/Rij rats and GAERS rats (Depaulis and Van Luijtelaar, 2005;Huang et al, 2012;Polack and Charpier, 2006;Shaw, 2004Shaw, , 2007Shaw et al, 2009;Van Luijtelaar et al, 2011) allowing the investigation of SWDs in this strain as well. Therefore, to validate and extend our previous results, in which we demonstrated the LPS induced increase in absence epileptic seizures in WAG/Rij rats (Kovács et al, 2006) we injected two doses of LPS (50 g/kg and 350 g/kg i.p.)…”

Pregabalin, Duloxetine, and Diazepam Selectively Modulate Acid-Induced Hyperalgesia and Anxio-Depressive Comorbidity in Rats

“…The results were expressed as a percentage of sucrose preference according to the following formula: preference (%) for sucrose over water (calculated as [sucrose intake/ total fluid intake] × 100%). The preference for sucrose solution is a reliable hedonic index in rats [12,19].…”

The zona incerta modulates spontaneous spike-wave discharges in the rat

“…The occurrence frequency of spontaneous SWDs is significantly reduced with the application of ethosuximide, valproic acid, and diazepam but increased with carbamazepine in a dose-dependent manner (Shaw 2007). Both ethosuximide and lamotrigine significantly not only reduce the occurrence frequency of SWDs, but also ameliorate comorbid anxiety and depression behaviors (Huang et al 2012;Shaw et al 2009). Although ZI neurons display different firing patterns during various cortical oscillations (including paroxysmal 5-to 9-Hz oscillations) in anesthetized rats (Bartho et al 2007), the involvement of incertal activities during SWDs, however, is currently unknown in freely moving rats.…”