title: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Kausar
authors.identifier: http://orcid.org/0000-0003-3163-2580
authors.initials: K
authors.lastname: Jahan
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Pillai
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Vohora
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects*; D005973:Glutamine / Q000378:metabolism; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D010649:Phenylalanine / Q000633:toxicity*; D011595:Psychomotor Agitation; D012640:Seizures / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D005973:Glutamine; D012701:Serotonin; D010649:Phenylalanine; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid
keywords: 5-HT; 6-Hz seizures; parachlorophenylalanine; sodium valproate