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. 1983 Dec;227(3):663-70.

Characterization of susceptibility to audiogenic seizures in ethanol-dependent rats after microinjection of gamma-aminobutyric acid (GABA) agonists into the inferior colliculus, substantia nigra or medial septum

G D Frye, T J McCown, G R Breese

Characterization of susceptibility to audiogenic seizures in ethanol-dependent rats after microinjection of gamma-aminobutyric acid (GABA) agonists into the inferior colliculus, substantia nigra or medial septum

G D Frye et al. J Pharmacol Exp Ther. 1983 Dec.

Abstract

The relative anticonvulsant potential of the gamma-aminobutyric acid (GABA) agonist, muscimol, was compared after microinjection into either the inferior colliculus, substantia nigra or medial septum of ethanol-dependent rats. Bilateral microinjection of muscimol (10-30 ng) into the inferior colliculus 15 to 60 min before testing suppressed all sound-induced seizure components (wild running, clonus and tonus) in rats withdrawn from ethanol for 6.5 to 8.5 hr. However, forelimb tremors were not altered. Audiogenic seizures were suppressed for at least 3 hr after muscimol (30 ng). In the medial septum and substantia nigra, microinjection of muscimol (30-100 ng) only partially reduced the tonic component of audiogenic seizures and exerted no effect on the frequency of wild running or clonus. GABA (10 micrograms) and two other GABA agonists [4,5,6,7-tetrahydroisoxazolo[5, 40c]pyridin-3-ol (THIP), 300 ng and chlordiazepoxide, 10-30 micrograms], microinjected into the inferior colliculus, also reduced audiogenic seizure susceptibility. However, 1, 3-butanediol, which suppresses ethanol withdrawal seizures after peripheral administration in rats, was inactive. The relative proconvulsant potential of the GABA antagonist, bicuculline methiodide, also was compared after microinjection into either the inferior colliculus, substantia nigra or medial septum of ethanol naive rats. In each animal, audiogenic seizure-like wild running, clonus and tonus were evoked by microinjecting bicuculline methiodide into the inferior colliculus at the rate of 6.0 ng/6 min. However, these reactions did not occur when bicuculline methiodide was applied at a slower rate (1.8 ng/6 min).(ABSTRACT TRUNCATED AT 250 WORDS)

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Figures

Fig. 1
Fig. 1
Graphic representation of the sites considered acceptable for microinjections into the inferior colliculus, substantia nigra and medial septum. Drawings of the inferior colliculus and medial septum were based on the atlas of Pellegiino et al., (1979), whereas the drawing of the substantia nigra was based on the atlas of Konig and Kippel (1963).
Fig. 2
Fig. 2
Effect of different doses of muscimol microinjected into the inferior colliculus, bilaterally, on susceptibility to audiogenic seizures during ethanol withdrawal. After 6.5 to 8.5 hr of withdrawal, ethanol-dependent rats were microinjected with muscimol or saline (SAL) solutions 15 min before being tested for susceptibility to audiogenic seizures. The total number of animals tested in each group are from left to right: 19,7, 8, 6 and 12. *P < .05 when compared with rats receiving microinjections of SAL.
Fig. 3
Fig. 3
Effect of time on suppression of susceptibility to audiogenic seizures during ethanol withdrawal of muscimol (30 ng) microinjected into the inferior colliculus. After 3.5 to 8.5 hr of withdrawal, ethanol-dependent rats were microinjected with muscimol or saline solutions at various times before being tested for susceptibility to audiogenic seizures. The total number of animals tested in each group are from left to right: 6, 5, 5, 6, 6 and 6. * P < .05 when compared with rats receiving microinjections of saline.
Fig. 4
Fig. 4
Effect of muscimol microinjected into the inferior colliculus, medial septum or substantia nigra on susceptibility to audiogenic seizures during ethanol withdrawal. After 6.5 to 8.5 hr of withdrawal, ethanol-dependent rats were microinjected with muscimol or saline (SAL) solutions 15 or 30 min before being tested for susceptibility to audiogenic seizures. The total number of animals tested in each group are from left to right: 6, 5, 10, 10, 11 and 12, respectively. *P < .05 when compared with rats receiving microinjections of SAL.
Fig. 5
Fig. 5
Effect of chlordiazepoxide, GABA and THIP microinjected into the inferior colliculus on susceptibility to audiogenic seizures during ethanol withdrawal. After 6.5 to 8.5 hr of withdrawal, ethanol-dependent rats were microinjected with muscimol or saline (SAL) solutions 15 min before being tested for susceptibility to audiogenic seizures. The total number of animals tested in each group are from left to right: 15, 6, 7,6 and 7. * P < .05 when compared with SAL microinjected controls.
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References

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