DSP-4 induced depletion of brain noradrenaline and increased 6-hertz psychomotor seizure susceptibility in mice is prevented by sodium valproate

Abstract

The central neurotransmitters assume a noteworthy part in the pathophysiology of epilepsy, noradrenaline is one of them. However, its role in 6 Hz induced psychomotor seizures is not known. The present study was, therefore, designed to investigate the role of noradrenaline (NA) in 6 Hz-induced psychomotor seizures in Swiss albino mice using N-2-Chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a well-known depletor of NA. The vehicle and DSP-4 treated mice were given 6 Hz stimulation. A sham treatment was utilized as a comparator and sodium valproate (SVP) was utilized as a reference anti-epileptic medication. Behavioral changes instigated by 6 Hz stimulation were described as the increased duration of Straub’s tail, stun position, twitching of vibrissae, forelimb clonus and increased rearing and grooming. DSP-4 administration further amplified the seizures and behavioral changes while pretreatment with SVP reduced the same in mice. Further, SVP pre-treatment also attenuated the ultra-structural changes observed in cortex and hippocampus of mice treated with DSP-4 and 6 Hz. Finally, the neurochemical estimation of NA in cortex and hippocampus confirmed the depletion of NA following DSP-4 and 6 Hz seizures. SVP pretreatment (but not post-treatment) protected the mice from 6 Hz seizures and attenuated the DSP-4 induced alterations of nor-adrenaline content in the mouse brain. The study indicates low brain NA content to enhance pharmacoresistant seizures in mice and demonstrates that SVP mediated protection against 6 Hz results possibly via modulation of NA content.