EFFECTS OF GABA(A) RECEPTORS ACTIVATION ON BRAIN GLUCOSE-METABOLISM IN NORMAL SUBJECTS AND TEMPORAL-LOBE EPILEPSY (TLE) PATIENTS - A POSITRON EMISSION TOMOGRAPHY (PET) STUDY .1. BRAIN GLUCOSE-METABOLISM IS INCREASED AFTER GABA(A) RECEPTORS ACTIVATION

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with position emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABA, receptors by systemic administration of the specific GABA, agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABA, receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.