Document Type

Dissertation

Publication Date

Fall 8-5-1959

Abstract

The effects of intracerebrally administered gamma-aminobutyric acid (GABA) and related compounds and the anticonvulsant activity of systemically and intracerebrally administered GABA were studied in mice. Systemic administration of GABA in doses of 1 g/kg or less did not induce neurotoxicity or exhibit anticonvulsant activity. Intracerebrally administered GABA, glycine, B-alanine and 5-amino-n-valeric acid elicited clonic movements followed by depression which increased in intensity as the doses of the compounds were increased when loss of righting reflex was used as the criteria of depression. GABA and Balanine were of equimolar potency and were more active than glycine and 5-amino-n-valeric acid which were equipotent. Intracerebrally administered 6-amino-n-caproic acid and 8-amino-n-caprylic acid induced clonus followed by tonic extensor seizures. The number of animals exhibiting tonic extensor seizures increased as the dose of the amino acids increased. 8-amino-n-caprylic acid was approximately ten times as potent as 6-amino-n-caproic acid on a molar basis. Clonus due to pentylenetetrazol (0.5% IV and 87.5 mg/kg SC) and convulsions due to minimal electroshock were prevented in low doses (20-60 ug/20 g) and potentiated in higher doses (80-160 ug/20 g) of intracerebrally administered GABA. Tonic extensor seizures and death induced by pentylenetetrazol (0.5% IV) were prevented by intracerebrally administered GABA. Clonus and tonic extensor seizures induced by caffeine (1% IV) and tonic convulsions induced by ammonium acetate (5% IV) were potentiated by intracerebrally administered GABA. Strychnine (1.25 mg/kg SC) convulsions or those induced by supramaximal electroshock were not altered by intracerebrally administered GABA.

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