Roles of gamma-aminobutyric acidB (GABA B) and gamma-hydroxybutyric acid receptors in hippocampal long-term potentiation and pathogenesis of absence seizures.

Abstract

Experiments were performed to examine the roles of gamma-aminobutyric acid(B) (GABA(B)) and gamma-hydroxybutyric acid (GHB) receptors in long-term potentiation (LTP) of the hippocampal CA1 region in vivo and in the genesis of the spike and wave discharges (SWDs) associated with absence seizures. When tetanic stimulation was delivered to the CA3 region, stable LTP was observed in the CA1 region in saline-treated mice. In mice treated with 5 mg/kg baclofen, the population spike amplitude was significantly potentiated by tetanic stimulation and the degree of potentiation was the same as that induced in saline controls. However, this potentiation decayed to the baseline level about 90 min after stimulation. The decay was reversed by pretreatment with 200 mg/kg P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35348), a selective GABA(B) receptor antagonist. In mice treated with 50 mg/kg gamma-butyrolactone (GBL), a prodrug of GHB, stable LTP was observed 90 min after tetanic stimulation and was greater than that in saline controls. GBL-induced potentiation of LTP was antagonized by 50 mg/kg NCS 382, a putative GHB receptor antagonist. Administration of baclofen (20 mg/kg) or GBL (70 mg/kg) induced absence-like seizures associated with 3-6 Hz SWDs, and CGP 35348 suppressed both baclofen- and GBL-induced SWDs. NCS 382 also attenuated SWDs induced by GBL and baclofen. These results suggest that baclofen and GHB have different effects on LTP in the CA1 region of the hippocampus in vivo, although they have a common mode of action on the thalamocortical functions related to the pathogenesis of absence seizures.

• Authors: M Aizawa, Y Ito, H Fukuda
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 20 Issue 10 Pg. 1066-70 (Oct 1997) ISSN: 0918-6158 [Print] Japan
• PMID: 9353566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-hydroxybutyric acid receptor
• Anticonvulsants
• Benzocycloheptenes
• GABA Agonists
• GABA Modulators
• Receptors, Cell Surface
• Receptors, GABA-B
• NCS 382
• Baclofen
• 4-Butyrolactone

Topics

• 4-Butyrolactone (pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Baclofen (pharmacology)
• Benzocycloheptenes (pharmacology)
• Electroencephalography
• Epilepsy, Absence (physiopathology)
• Female
• GABA Agonists (pharmacology)
• GABA Modulators (pharmacology)
• Hippocampus (drug effects, physiopathology)
• Long-Term Potentiation (drug effects, physiology)
• Male
• Mice
• Receptors, Cell Surface (physiology)
• Receptors, GABA-B (physiology)