Abstract

Gamma-hydroxybutyric acid (GHB) is a naturally occurring metabolite of GABA which has the ability to produce petit mal-like seizures when administered to animals. We have characterized the biochemical and neurophysiologic ontogeny of this compound, identified specific binding sites for GHB in brain, investigated metabolic sources for GHB in brain other than GABA, and shown that GABAergic mechanisms may play a role in GHB-induced seizures while dopaminergic and cholinergic mechanisms do not. We propose to continue these various lines of investigation into the function of GHB in brain and the mechanism by which it produes petit mal-like seizures. There are three hypotheses to be tested. First that GHB-induced hypothermia is responsible for part or all of the EEG effects of this compound. Second that GABAergic mechanisms play a role in the genesis of GHB-induced seizure. The third hypotheses is that there is a source for GHB in brain additional to GABA. The relation of GHB seizures to GHB-induced hypothermia will therefore be determined. GABA-GHB interaction will be exmained by detail neurophysiologic and ontogeny studies of GABA agonists and GHB as well as by receptor binding studies designed to characterize GHB-GABA interaction at the level of the receptor. The relation of GHB to a possible non-GABA precursor, 1,4 butanediol will be characterized by gas chromatographic/mass spectroscopic techniques.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS017117-04A2
Application #
3397348
Study Section
Neurology A Study Section (NEUA)
Project Start
1981-04-01
Project End
1989-01-31
Budget Start
1986-02-01
Budget End
1987-01-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Motte, J; Fernandes, M J; Baram, T Z et al. (1998) Spatial and temporal evolution of neuronal activation, stress and injury in lithium-pilocarpine seizures in adult rats. Brain Res 793:61-72
Banerjee, P K; Olsen, R W; Tillakaratne, N J et al. (1998) Absence seizures decrease steroid modulation of t-[35S]butylbicyclophosphorothionate binding in thalamic relay nuclei. J Pharmacol Exp Ther 287:766-72
Banerjee, P K; Tillakaratne, N J; Brailowsky, S et al. (1998) Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats. Exp Neurol 154:213-23
Snead 3rd, O C (1996) Presynaptic GABAB-and gamma-hydroxybutyric acid-mediated mechanisms in generalized absence seizures. Neuropharmacology 35:359-67
Snead 3rd, O C (1996) Relation of the [3H] gamma-hydroxybutyric acid (GHB) binding site to the gamma-aminobutyric acidB (GABAB) receptor in rat brain. Biochem Pharmacol 52:1235-43
Snead 3rd, O C (1996) Antiabsence seizure activity of specific GABAB and gamma-Hydroxybutyric acid receptor antagonists. Pharmacol Biochem Behav 53:73-9
Snead 3rd, O C (1995) Basic mechanisms of generalized absence seizures. Ann Neurol 37:146-57
Banerjee, P K; Snead 3rd, O C (1995) Thalamic NMDA receptors in the gamma-hydroxybutyrate model of absence seizures: a cerebral microinjection study in rats. Neuropharmacology 34:43-53
Banerjee, P K; Snead 3rd, O C (1995) Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): a possible mechanism for the generation of absence-like seizures induced by GH J Pharmacol Exp Ther 273:1534-43
Banerjee, P K; Snead 3rd, O C (1994) Thalamic mediodorsal and intralaminar nuclear lesions disrupt the generation of experimentally induced generalized absence-like seizures in rats. Epilepsy Res 17:193-205

Showing the most recent 10 out of 32 publications