title: Hippocampal orexin receptors inactivation reduces PTZ induced seizures of male rats.
abstract: BACKGROUND
  Orexin has been shown to be involved in a number of physiological and behavioral processes including, feeding and metabolism, reward, nociception, and anxiety. Furthermore, orexin can cause increased neuronal excitability that gives rise to epileptic activity. The distribution of orexin receptor expression in the hippocampus, suggests a possible importance of orexin in the control of seizures in the temporal lobe epilepsy. Therefore, in this study, the effect of hippocampal orexin 1 and 2 receptors on seizure and glutamate and GABA (gamma-aminobutyric acid) contents was explored.
  
  
  METHODS
  Orexin 1 receptor (OX1R) antagonist (SB) and OX2R antagonist (TCS) were administrated bilaterally through separate cannulae into both hippocampi. Behavioral convulsions were provoked by intravenous pentylenetetrazol (PTZ) application model. The amount of total hippocampal glutamate and GABA contents was then measured by a biochemical method.
  
  
  RESULTS
  SB (50 nmol) infusion reduced seizure stage, duration and decreased glutamate while GABA content was increased. SB (200 nmol) also reduced seizure stage, duration and glutamate content, without change of GABA content. TCS (20 nmol) infusion reduced seizure stage and duration without concomitant change in glutamate and GABA contents. Further, TCS (40 nmol) did neither affect the seizure nor the GABA, while decreased glutamate content. Co-administration of SB (50 nmol) with TCS (40 nmol) and also SB (200 nmol) with TCS (40 nmol) reduced seizure stage, duration and glutamate, but increased GABA content.
  
  
  CONCLUSIONS
  It is concluded that OX1R and OX2R antagonists reduce convulsive intensity, partially through alterations of hippocampal glutamate and GABA contents.
authors.affiliation: Faculty of Biology, Damghan University, Damghan, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Goudarzi
authors.affiliation: Faculty of Biology, Damghan University, Damghan, Iran. Electronic address: elahdadi@du.ac.ir.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Elahdadi Salmani
authors.affiliation: Faculty of Biology, Damghan University, Damghan, Iran.
authors.forename: Taghi
authors.initials: T
authors.lastname: Lashkarbolouki
authors.affiliation: Faculty of Biology, Damghan University, Damghan, Iran.
authors.forename: Iran
authors.initials: I
authors.lastname: Goudarzi
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology*; D064446:Orexin Receptors / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; C572065:1-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-3,3-dimethyl-2-((4-pyridinylmethyl)amino)-1-butanone; D001583:Benzoxazoles; D003292:Convulsants; D007546:Isoquinolines; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D011725:Pyridines; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014508:Urea; D010433:Pentylenetetrazole
keywords: GABA; Glutamate; Orexin receptor antagonist; Pentylenetetrazol; Seizures