Effects of acute and subacute treatment with ergot drugs on the GABA system in specific brain regions

Abstract

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.