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

In the present study, alterations of the general GABA, GABAA and GABAB receptors in the cerebral cortex of the epileptic rat and the therapeutic application of Bacopa monnieri were investigated.Scatchard analysis of [3H]GABA, [3H]bicuculline and [3H]baclofen in the cerebral cortex of the epileptic rat showed significant decrease in Bmax (P < 0.001) compared to control. Real Time PCR amplification of GABA receptor subunits such as GABAA？1, GABAAγ, GABAAδ, GABAB and GAD where down regulated (P < 0.001) in epileptic rats. GABAA？5 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.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.GABA is formed within GABAergic axon terminals and released into the synapse, where it acts at one of two types of receptor GABAA which controls chloride entry into the cell, and GABAB, which increases potassium conductance, decreases calcium entry, and inhibits the presynaptic release of other neurotransmitters [1,2]. Temporal lobe epilepsy (TLE) is considered the most common epileptic syndrome and it is estimated that approximately 80% of patients with partial seizures have temporal lobe epilepsy [3]. The effect of pilocarpine treatment, which is characterized by generalized convulsive status epilepticus in rodents, well represents the characteristic neuropathological findings in the brain regions of the patients with TLE epilepsy [4]. Imbalance between excitatory and inhibitory synaptic transmission in key brain areas are implicated in the pathophysiology of TLE, in which there is a decrease in the GABA mediated inhibition. TLE seizures