The periaqueductal grey is a critical site in the neuronal network for audiogenic seizures: modulation by GABA(A), NMDA and opioid receptors.
The nuclei comprising the neuronal network for audiogenic seizures (AGS) are located primarily in the brainstem. Previous studies suggested a role for the periaqueductal grey (PAG) in the AGS network. The present study evaluated this possibility in genetically-epilepsy prone rats (GEPR-9s) by examining the effects of bilateral focal microinjection of a competitive NMDA receptor antagonist (DL-2-amino-7-phosphonoheptanoic acid (AP7), 1 and 5 nmol/side), a GABA(A) agonist (gaboxedol (THIP), 10 and 15 nmol) or an opioid peptide receptor antagonist (naloxone, 5 nmol) into PAG, based on the proposed role of these receptors in PAG neurotransmission. Blockade of NMDA receptors by AP7 (both doses) or activation of GABA(A) receptors with THIP (15 nmol/side) in the PAG suppressed AGS susceptibility. Naloxone displayed a seizure-suppressant effect that was delayed and incomplete. The seizure suppressant effect of AP7 or naloxone, unlike THIP, was observed at doses that did not produce motor quiescence. These data suggest that the PAG is a requisite nucleus in the neuronal network for AGS in GEPR-9s and that GABA(A), opioid peptide and NMDA receptors in the PAG modulate AGS propagation.
N'Gouemo
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Department of Pharmacology Southern Illinois University School of Medicine, Springfield 62794-9629, USA.
Faingold
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects*; D012640:Seizures / Q000235:genetics / Q000503:physiopathology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D058785:GABA-A Receptor Agonists; D007555:Isoxazoles; D009292:Narcotic Antagonists; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D009270:Naloxone; D015763:2-Amino-5-phosphonovalerate; C015542:gaboxadol; C031231:2-amino-7-phosphonoheptanoic acid