Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A

ABSTACT: BACKGROUND: Gamma amino butyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tones that counter balances neuronal excitation. When this balance is perturbed, seizures may ensue. METHODS: In the present study, alterations of the general GABA, GABA(A )and GABA(B )receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated. RESULTS: Scatchard analysis of [(3)H]GABA, [(3)H]bicuculline and [(3)H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in B(max )(P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABA(Aά1), GABA(Aγ), GABA(Aδ), GABA(B )and GAD where down regulated (P < 0.001) in epileptic rats. GABA(Aά5 )subunit and Cyclic AMP responsible element binding protein were up regulated. Confocal imaging study confirmed the decreased GABA receptors in epileptic rats. Epileptic rats have deficit in radial arm and Y maze performance. CONCLUSIONS: Bacopa monnieri and Bacoside-A treatment reverses epilepsy associated changes to near control suggesting that decreased GABA receptors in the cerebral cortex have an important role in epileptic occurrence; Bacopa monnieri and Bacoside-A have therapeutic application in epilepsy management.