Role of the amygdala in ethanol withdrawal seizures.
Ethanol withdrawal (ETX) after induction of ethanol dependence results in a syndrome that includes enhanced seizure susceptibility. During ETX in rodents, generalized audiogenic seizures (AGS) can be triggered by intense acoustic stimulation. Previous studies have implicated specific brainstem nuclei in the neuronal network that initiates and propagates AGS during ETX. Although ethanol and ETX are known to affect amygdala neurons, involvement of the amygdala in the network subserving AGS is unclear. Since ethanol and ETX affect N-methyl-d-aspartate (NMDA) receptors in the amygdala, the present study evaluated the effect of focally microinjecting a NMDA antagonist into the amygdala of rats treated with a binge protocol (intragastric administration of ethanol 3 times daily for 4 days). Separate experiments examined extracellular neuronal firing in the amygdala. Cannulae or microwire electrodes were chronically implanted into the amygdala, and changes in seizure behaviors and/or extracellular action potentials were evaluated. Bilateral focal microinjection of a NMDA antagonist, 2-amino-7-phosphonoheptanoate (AP7), into either central nucleus or lateral nucleus of the amygdala (LAMG) significantly reduced AGS. The doses of AP7 and time course of effect were similar in each site, suggesting that both amygdala nuclei participate in the AGS network. Acoustic responses of LAMG neurons were significantly decreased 1 h after the first ethanol dose and also during ETX, as compared to pre-binge controls. However, LAMG neurons consistently exhibited rapid tonic firing during the generalized tonic convulsions of AGS. These findings suggest a critical role of the amygdala in the ETX seizure network in generating tonic convulsions during AGS.
Feng
Hua-Jun
HJ
Department of Pharmacology, Southern Illinois University School of Medicine, PO Box 19629, Springfield, IL 62794-9629, USA.
Yang
Li
L
Faingold
Carl L
CL
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D020270:Alcohol Withdrawal Seizures / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004569:Electroencephalography; D000431:Ethanol / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D000431:Ethanol; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid