[P2-99] Study of Characteristics and Antiepileptic Drug Response in Lister-Hooded Rats with Audiogenic Seizure
The Lister-Hooded (LH) rat is a commonly used strain to model mental illness-like cognitive deficits. Recently, acoustically elicited behavior was reported in LH rats, although very little is known about the pathological conditions of acoustically elicited behavior in LH rats, especially in childhood rats. This study analyzes the mechanisms of acoustically elicited behavior in juvenile LH rat.
LH rats (22-26 days old) were implanted with EEG electrodes and exposed to continuous acoustic stimulation (7 kHz, 110 dB). We then evaluated the efficacy of antiepileptic drugs (diazepam, phenytoin, levetiracetam, and dextromethorphan) against acoustically elicited behavior.
The type of acoustically elicited behavior was stereotypical and consisted of wild running followed by tonic posture with screaming. When tonic posture appeared, EEG recordings indicated an increase in low-amplitude fast activity, which was similar to findings in epileptic tonic seizures in human. These acoustically elicited behaviors were completely suppressed by diazepam administration (0.25 mg/kg), as well as high-dose levetiracetam (50 mg/kg) and dextromethorphan (25 mg/kg). However, phenytoin (50 mg/kg) resulted in incomplete suppression.
Generalized convulsive seizures are mediated by the “centrencephalon,” which includes the brainstem reticular formation. The audiogenic seizure neuronal network involves the brainstem auditory nuclei up to the inferior colliculus, where a deficit in GABA-mediated inhibition causes excessive acoustically evoked neuronal firing. These findings suggest that acoustically elicited behavior in LH rats corresponds with audiogenic seizures in humans, and GABAergic dysfunction might be responsible for the development of audiogenic seizures.
LH rats (22-26 days old) were implanted with EEG electrodes and exposed to continuous acoustic stimulation (7 kHz, 110 dB). We then evaluated the efficacy of antiepileptic drugs (diazepam, phenytoin, levetiracetam, and dextromethorphan) against acoustically elicited behavior.
The type of acoustically elicited behavior was stereotypical and consisted of wild running followed by tonic posture with screaming. When tonic posture appeared, EEG recordings indicated an increase in low-amplitude fast activity, which was similar to findings in epileptic tonic seizures in human. These acoustically elicited behaviors were completely suppressed by diazepam administration (0.25 mg/kg), as well as high-dose levetiracetam (50 mg/kg) and dextromethorphan (25 mg/kg). However, phenytoin (50 mg/kg) resulted in incomplete suppression.
Generalized convulsive seizures are mediated by the “centrencephalon,” which includes the brainstem reticular formation. The audiogenic seizure neuronal network involves the brainstem auditory nuclei up to the inferior colliculus, where a deficit in GABA-mediated inhibition causes excessive acoustically evoked neuronal firing. These findings suggest that acoustically elicited behavior in LH rats corresponds with audiogenic seizures in humans, and GABAergic dysfunction might be responsible for the development of audiogenic seizures.