Trazodone increases seizures in a genetic WAG/Rij rat model of absence epilepsy while decreasing them in penicillin-evoked focal seizure model

Abstract

AimPsychiatric disorders, especially depression and anxiety, are among the most disabling comorbidities in patients with epilepsy, and they are difficult to treat because many antidepressants cause proconvulsive effects. Thus, it is important to identify the seizure risks associated with antidepressants. Trazodone is one of the most frequently prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs for the treatment of depression and anxiety. The aim of the present study was to evaluate the effects of trazodone on epileptiform activity in a penicillin-evoked focal seizure model in Wistar rats and in a genetic absence epilepsy model in Wistar Albino Glaxo/Rijswijk strain (WAG/Rij) rats. MethodsTrazodone at 5-, 10-, and 30-mg/kg doses was injected intraperitoneally in Wistar rats 30 min after penicillin injection, and spike frequency and amplitude of penicillin-induced epileptiform activity were evaluated. In a separate experimental model, the same trazodone doses were injected in WAG/Rij rats to elucidate their effects on number, duration, and amplitude of spike-and-wave discharges (SWDs) and on depression–anxiety like behavior. In both experimental groups, after trazodone injections recordings were made for 3 h. Depression–anxiety like behaviors in WAG/Rij rats were examined using forced swim test and open-field test. ResultsTrazodone at 10- and 30-mg/kg doses significantly reduced the frequency of penicillin-induced epileptiform activity without changing the amplitude. Trazodone at a 5-mg/kg dose had no effect on either frequency or amplitude of epileptiform activity. Trazodone at all doses significantly increased number and duration of SWDs without changing the amplitude. In addition, all doses of trazodone decreased the number of squares crossed and duration of grooming in open-field test, and reduced swimming time activity and increased immobility time in forced swim test. ConclusionOur results suggest that depending on the dose used, trazodone had an anticonvulsant effect or no effect on penicillin-evoked focal seizure model, but all trazodone doses resulted in proconvulsant and depression–anxiety like behavior in WAG/Rij rats, which represent a genetic absence model of epilepsy.