Serotonin depletion increases seizure susceptibility and worsens neuropathological outcomes in kainate model of epilepsy

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Maia, GH (Author) Other; Brazete, CS (Author) Other; Soares, JI (Author) Other; Luz, LL (Author) Other; Lukoyanov, NV (Author) FMUP

Journal

Title: Brain Research Bulletin

Vol. 134

Pages: 109-120

ISSN: 0361-9230

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 21 Citations

Scopus - 22 Citations

Other information

Authenticus ID: P-00N-31R

DOI: 10.1016/j.brainresbull.2017.07.009

Abstract (EN): Serotonin is implicated in the regulation of seizures, but whether or not it can potentiate the effects of epileptogenic factors is not fully established. Using the kainic acid model of epilepsy in rats, we tested the effects of serotonin depletion on (1) susceptibility to acute seizures, (2) development of spontaneous recurrent seizures and (3) behavioral and neuroanatomical sequelae of kainic acid treatment. Serotonin was depleted by pre treating rats with p-chlorophenylalanine. In different groups, kainic acid was injected at 3 different doses: 6.5 mg/kg, 9.0 mg/kg or 12.5 mg/kg. A single dose of 6.5 mg/kg of kainic acid reliably induced status epilepticus in p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats. The neuroexcitatory effects of kainic acid in the p-chlorophenylalanine-pretreated rats, but not in saline-pretreated rats, were associated with the presence of tonic-clonic convulsions and high lethality. Compared to controls, a greater portion of serotonin-depleted rats showed spontaneous recurrent seizures after kainic acid injections. Loss of hippocampal neurons and spatial memory deficits associated with kainic acid treatment were exacerbated by prior depletion of serotonin. The present findings are of particular importance because they suggest that low serotonin activity may represent one of the major risk factors for epilepsy and, thus, offer potentially relevant targets for prevention of epileptogenesis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12