THE EFFECT OF INJECTION OF SERTRALIN ON SPIKE-WAVE- DISCHARGES AND STEREOTYPIC BEHAVIOR OF GENETIC ABSENCE EPILEPSY RATS FROM STRASBOURG

Abstract Background Absence epilepsy is characterized by non-convulsive generalized seizures and typical bilateral synchronous spike-wave discharges (SWDs) on EEG. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are known as experimental animals used for the absence epilepsy model, produced from the Wistar strain in the early 1980s. The effect of serotonin on absence epileptic seizures is unclear. In rats, stereotypic behaviors include extremity flexion and extension without displacement, grooming, chewing, sniffing, orofacial movements, head weaving, etc. In a study, GAERS demonstrated more stereotypic activities than naive Wistar rats. Serotonergic and dopaminergic transmission may also play a role in stereotypical behaviors. Aims & Objectives The aims of this study were to evaluate the SWDs analyses of the GAERS during EEG recordings and examination of their stereotypical behaviors in the locomotor activity cage by administering sertraline, a selective serotonin reuptake inhibitor antidepressant. Method After the recording electrodes were placed using stereotaxic surgery, adult GAERS male rats were divided into two groups (n = 7). EEG recordings were obtained five consecutive days from 09:00 to 12:00, followed by 15 minutes of locomotor activity recording. After the first 60 minutes of the EEG baseline recording; 10 mg/kg intraperitoneal sertraline and vehicle were given to the treatment and control groups, respectively. EEG recordings were continued for 2 hours after the injection. Stereotypic behaviors were analyzed in the locomotor activity cage for 5 days. At the end of the fifth day, the elevated plus maze test was applied to the rats. The experimental groups were compared using 2-way ANOVA and t-test. Results The cumulative duration of SWDs resulted in terms of percentage change compared to baseline in the first 20 minutes after injection significantly less in the sertraline group (54.6 ± 13.6) than in the control group (94.2 ± 8.5) (p=0.03). When SWDs were evaluated generally, no significant difference was found between groups of seizure numbers, average and cumulative durations. The locomotor activity test showed no significant stereotypic behavior differences. The elevated plus maze test showed that rats injected with sertraline for 5 days spent more time in the open field than the control group. Discussion & Conclusion The impact of sertraline on SWDs observed in absence seizures has not been studied before in the literature. Although sertraline reduced the cumulative SWD duration in the early period; analysis of the total SWDs duration showed that parenteral administration of sertraline at the dose (10 mg/kg) and duration (5 days) tested did not affect absence seizures and stereotypic behaviors; however, it resulted in a decrease in anxiety behaviors. Further studies are needed to explain the effect of serotonin on SWDs of absence epilepsy and the stereotypic behaviors of GAERS by using other drugs affecting serotonin metabolism at different doses. This study suggested that the anxiety behaviors that occurred in GAERS have a weak relationship with stereotypical behaviors. Therefore, it might be worthwhile to investigate different neurotransmitters such as GABA, glutamine, and dopamine in this field.