Effects of acute and subacute treatment with ergot drugs on the GABA system in specific brain regions.
The effect of dihydroergotoxine and dihydroergotamine on gamma-aminobutyric acid (GABA) levels, the aminooxyacetic acid (AOAA)-induced accumulation of GABA, and the in vitro activity of L-glutamate decarboxylase (GAD) have been examined in various regions of rat brain. Dihydroergotoxine (1 mg kg-1) decreased the concentration of GABA and enhanced the AOAA-induced accumulation of GABA in the caudate nucleus and cingulate cortex. Dihydroergotoxine 10.0 mg kg-1 decreased the AOAA-induced accumulation of GABA in the substantia nigra. The repeated treatment with dihydroergotoxine, 0.05 mg kg-1 for eight days, also decreased the concentration of GABA in the cingulate cortex and diminished the AOAA-induced accumulation of GABA in the substantia nigra. The administration of 0.1 mg kg-1, but not higher doses; of dihydroergotamine, enhanced the AOAA-induced accumulation of GABA in the cingulate cortex. Dihydroergotamine (10.0 mg kg-1) decreased the concentration of GABA in the cingulate cortex and increased the AOAA-induced accumulation of GABA in the caudate nucleus. The activity of GAD in the cingulate cortex, but not in the caudate nucleus, was enhanced after a high dose of dihydroergotamine. Observed increases in the AOAA-induced accumulation of GABA indicate that dihydroergotoxine and dihydroergotamine in at least some brain areas cause an apparent increase in GABA synthesis in vivo, which is presumably a compensatory phenomenon due to a diminished GABAergic transmission under the influence of these drugs.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004087:Dihydroergotamine / Q000494:pharmacology; D004088:Dihydroergotoxine / Q000494:pharmacology; D004876:Ergot Alkaloids / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004876:Ergot Alkaloids; D004088:Dihydroergotoxine; D000625:Aminooxyacetic Acid; D004087:Dihydroergotamine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase