Glutamate in the inferior colliculus plays a critical role in audiogenic seizure initiation.
Alterations of excitant amino acid (EAA) action are implicated in seizure susceptibility in the genetically epilepsy-prone rat (GEPR). The inferior colliculus (IC) is critical for audiogenic seizure (AGS) initiation in the GEPR. The present study observed that bilateral microinjection into the IC of L-canaline, a glutamate synthesis inhibitor, decreased AGS severity in the GEPR and also decreased potassium-evoked release of glutamate from IC slices. Bilateral microinjection of NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP7) or 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) into IC blocked AGS, and an antagonist at non-NMDA EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), also blocked AGS. NMDA receptor antagonists were 5-200 times more effective than CNQX. Microinjection of a non-competitive NMDA receptor antagonist, dizocilpine (MK-801), into IC had little effect except with very high doses. Microinjection of CPP or AP7 into the IC blocked AGS at considerably lower doses as compared to pontine reticular formation (PRF). However, MK-801 attenuated AGS when microinjected into PRF at doses that were ineffective in IC. Systemically administered CPP blocked AGS and significantly reduced IC neuronal firing in the behaving GEPR, suggesting an important action of systemically administered NMDA receptor antagonists on brainstem auditory nuclei critical to AGS. The present results support a critical role for glutamate acting, in part, through NMDA receptors in IC in initiation of AGS.
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794.
C L
CL
Faingold
D K
DK
Naritoku
C A
CA
Copley
M E
ME
Randall
A
A
Riaz
C A
CA
Anderson
S P
SP
Arnerić
D000161:Acoustic Stimulation; D000613:Aminobutyrates / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005971:Glutamates / Q000032:analysis* / Q000502:physiology; D018698:Glutamic Acid; D007245:Inferior Colliculi / Q000737:chemistry* / Q000187:drug effects / Q000503:physiopathology; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology*; D013997:Time Factors
D000613:Aminobutyrates; D005971:Glutamates; D018698:Glutamic Acid; C001926:canaline