The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats


ŞAHİN B., ÖZDEMİR E., Gumus E., ERGÜL M., TAŞKIRAN A. Ş.

NEUROLOGICAL RESEARCH, vol.44, no.9, pp.786-796, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 9
  • Publication Date: 2022
  • Doi Number: 10.1080/01616412.2022.2064700
  • Journal Name: NEUROLOGICAL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE
  • Page Numbers: pp.786-796
  • Keywords: 5-HT receptor, 5-HT7, SB-269970, seizure, c-Fos, GABA, GAMMA-AMINOBUTYRIC-ACID, CEREBROSPINAL-FLUID, SEROTONIN, MODELS, BRAIN, STIMULATION, INHIBITION, MODULATION, SB-258741, RELEASE
  • Sivas Cumhuriyet University Affiliated: Yes

Abstract

Objectives Recently, studies have demonstrated that serotonin type 7 receptors (5-HT7) have conflincting effects on neuronal excitability in different brain regions. However, the effect of 5-HT7 on seizures has not been exactly elucidated yet. Therefore, our aim in this study was to investigate the effects of 5-HT7 antagonist SB-269970 on pentylenetetrazole (PTZ) induced fully kindled rats. Methods In the study, 32 adult male Wistar Albino rats (weighing 220-260 g) were used. Rats were injected with PTZ (35 mg/kg) intraperitoneally every other day to generate kindling model. 5-CT (0.1 mg/kg) and SB-269970 (1 mg/kg) were administered 30 min before acute seizure induction with PTZ (35 mg/kg). Seizure stages were determined according to the Racine scale. After electrocorticography (ECoG) recordings of seizure-induced rats were obtained, the animals were sacrificed by decapitation. The hippocampal GABA levels were determined by ELISA kit and the number of c-Fos positive neurons in the hippocampal dentate gyrus (DG), CA1 and CA3 areas were measured by immunohistochemical method. Results The results showed that SB-269970 reduced the number of spikes, percent seizure duration and duration of generalized tonic-clonic seizures (dGTCS), while increasing the onset time of generalized tonic-clonic seizures (oGTCS). The hippocampal GABA levels were significantly increased in the SB-269970 group compared with the PTZ group. In addition, SB-269970 reduced the number of c-Fos positive cells in hippocampal CA1 area. Discussion 5-HT7 antagonist SB-269970 displays anticonvulsant effects on PTZ-induced seizures in fully kindled rats and these effects may be related to GABAergic activity in the hippocampus.