GABAergic modulation of inferior colliculus excitability: role in the ethanol withdrawal audiogenic seizures.
The role of the inferior colliculus and GABAeric transmission within this structure in the development of susceptibility to sound-induced seizures in ethanol-dependent rats was examined. Ethanol-dependent rats with bilateral electrolytic lesions which destroyed approximately 50.0 +/- 6.4% of the inferior colliculus failed to exhibit susceptibility to sound-induced seizures. However, comparable medial geniculate body lesions (82.7 +/- 2.7% complete) did not alter wild running, slightly reduced tonus and actually increased clonus susceptibility in rats treated similarly with ethanol. As reported previously, bilateral injection of either muscimol (43-263 pmol/site) or racemic baclofen (520-1580 pmol/site) into the inferior colliculus also suppressed seizure susceptibility. Other studies in ethanol-naive animals found that bilateral microinfusion of (+)-bicuculline methiodide (2 or 20 pmol/min for up to 5 min) into the inferior colliculus induced wild running and clonus closely resembling sound-induced seizure responses in ethanol-dependent rats. Although similar microinjections of (+)-bicuculline methiodide (0.4 pmol/min for 5 min) into the inferior colliculus did not induce seizure activity directly, an increased susceptibility to sound-induced seizures was observed. Electrolytic lesions of the medial geniculate body did not block wild running responses induced by (+)-bicuculline methiodide, but slightly reduced clonus. Five-minute infusions of picrotoxin (200 pmol/min), Ro5-3663 (2000 pmol/min), kainic acid (20 or 200 pmol/min), strychnine (2000 pmol/min) or carbachol 2000 pmol/min) into the inferior colliculus of ethanol-naive rats all induced bicuculline-like seizures. Seizures induced by bicuculline methiodide, picrotoxin or Ro5-3663 occurred within 5 min after the start of infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
D000161:Acoustic Stimulation; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D005829:Geniculate Bodies / Q000502:physiology; D007245:Inferior Colliculi / Q000502:physiology*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D009118:Muscimol; D000431:Ethanol; C017069:bicuculline methiodide; C022193:Ro 5-3663; D001418:Baclofen; D007608:Kainic Acid; D001640:Bicuculline