Determination of amino acids and monoamine neurotransmitters in caudate nucleus of seizure-resistant and seizure-prone BALB/c mice.
Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.
Vriend
J
J
Department of Anatomy, University of Manitoba, Winnipeg, Canada.
Alexiuk
N A
NA
Green-Johnson
J
J
Ryan
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism*; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012640:Seizures / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D015306:Biogenic Monoamines; D005971:Glutamates; D006834:Hydrazines; D005973:Glutamine; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D018698:Glutamic Acid; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid