Parachlorophenylalanine‐induced 5‐HT depletion alters behavioral and brain neurotransmitters levels in 6‐Hz psychomotor seizure model in mice

Abstract

The present study was designed to investigate the role of serotonin and other neurotransmitters namely dopamine (DA), histamine, nor-epinephrine (NE), glutamate, and γ-aminobutyric acid (GABA) in the 6-Hz-induced psychomotor seizures in Swiss albino mice. Parachlorophenylalanine (PCPA, 300 mg/kg/day, i.p for 3 days)-treated mice were given 6-Hz stimulation. Sodium valproate (SVP) (200 mg/kg/day, p.o for 3 days) was used as a reference antiepileptic drug. The behavioral changes induced by 6 Hz including increased rearing and grooming, Straub's tail, behavioral arrest, stun position were amplified by PCPA. The 6-Hz-induced seizures were accompanied by reduced brain 5-HT, DA, NE, histamine, GABA, and enhanced glutamate levels. PCPA facilitated further reduction of endogenous 5-HT and DA levels but not NE, histamine, GABA, and glutamate levels. Pre- and post-treatment with SVP protected the mice from 6-Hz seizures and attenuated PCPA-induced changes in the levels of 5-HT and DA in the mice brain suggesting the protective effect of SVP in the pharmacoresistant model of epilepsy involving mainly serotonergic mechanism. However, the study also suggests modulation of other neurotransmitters both in 6-Hz psychomotor seizures and in the action of SVP against such seizures.

Central histaminergic signalling, neural excitability and epilepsy

“…Studies on MES‐induced generalized tonic–clonic seizures have also found that histamine decreased in the cortex, hippocampus, brainstem, and hypothalamus in TMN‐lesioned rats (Jin et al, 2007). Moreover, reductions in brain histamine were observed following amygdala kindling‐induced focal seizures using secondary generalized seizure rats, transauricular kindling rats, and 6‐Hz stimulation mice (Jahan et al, 2017; Kamei et al, 1998; Li et al, 2006). Research has also detected reduced histamine level in blood (Gholipoor et al, 2013; hyperthermia‐induced febrile seizure mice) and the hypothalamus (Tuomisto et al, 2003; audiogenic DBA/2 mice).…”

“…More recently, both clinical and preclinical research suggests that histamine in the CNS plays an important role in the pathogenesis of epilepsy. For instance, a decline in histamine amount was found in the temporal neocortex of pharmaco-resistant mesial temporal lobe epilepsy (MTLE) patients (Bañuelos-Cabrera et al, 2016) and in many animal epilepsy models (Jahan et al, 2017;Kamei et al, 1998;Li et al, 2006). Histamine H 1 receptor antagonists have demonstrated a seizure-promoting effect in several clinical cases (Labarinas et al, 2018;Yokoyama et al, 1993Yokoyama et al, , 2012.…”

Formulation and evaluation of nano lipid formulation containing CNS acting drug: molecular docking, in-vitro assessment and bioactivity detail in rats

“…The 5-HT level was estimated at fluorescence excitation (360 nm)/emission (470 nm). The monoamine levels were expressed as pg/mg tissue [30,31].…”

Serotonergic mechanisms in the 6-Hz psychomotor seizures in mice

“…Recently, we reported the role of monoamines in 6Hz-induced psychomotor seizures and demonstrated that PCPA induced 5-HT depletion in whole brain and aggravated 6Hz-psychomotor seizures in mice. 10 In the present work, we aimed to investigate the effect of 5-HT depletion in cortex and hippocampus (brain regions relevant for epilepsy) by PCPA on 6 Hz psychomotor seizures in mice and possible protection by sodium valproate (SVP). The drug is reported to produce anticonvulsant effects against 6 Hz seizures in mice and to alter 5-HT levels in pentylenetetrazole-induced kindled mice.…”