Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: effect of Bacopa monnieri and bacoside-A.
OBJECTIVE
Gamma-aminobutyric acid A receptors are the principal mediators of synaptic inhibition in striatal neurons and play an important role in preventing the spreading of seizures through the striatum. In the present study, effect of Bacopa monnieri (L.) Pennel and its active component bacoside-A on spatial recognition memory deficit and alterations of GABA receptor in the striatum of epileptic rats were investigated.


METHODS
Total GABA and GABA(A) receptor numbers in the control and epileptic rats were evaluated using [(3)H]GABA and [(3)H]bicuculline binding. GABA(Aalpha1,) GABA(Aalpha5,) GABA(Agamma3) and GABA(Adelta) gene expressions were studied. Behavioral performance was assed using Y-maze.


RESULTS
Scatchard analysis of [(3)H]GABA and [(3)H]bicuculline in the striatum of epileptic rats showed significant decrease in B(max) compared to control. Real-Time PCR amplification of GABA(A) receptor subunits such as GABA(Aalpha1,) GABA(Aalpha5) and GABA(Adelta), were down regulated (p<0.001) in the striatum of epileptic rats compared to control. Epileptic rats have deficit in Y-maze performance. Bacopa monnieri and bacoside-A treatment reversed these changes to near control.


CONCLUSIONS
Our results suggest that decreased GABA receptors in the striatum have an important role in epilepsy associated motor learning deficits and Bacopa monnieri and bacoside-A has a beneficial effect in the management of epilepsy.
Mathew
Jobin
J
Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Cochin, Kerala, India.
Soman
Smijin
S
Sadanandan
Jayanarayanan
J
Paulose
Cheramadathikudyil Skaria
CS
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D034681:Bacopa; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001640:Bicuculline / Q000378:metabolism; D001667:Binding, Competitive; D002220:Carbamazepine / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D018756:GABA Antagonists / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010862:Pilocarpine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000927:Anticonvulsants; D018756:GABA Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D012503:Saponins; D014315:Triterpenes; C500175:bacoside A; D010862:Pilocarpine; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline