Down-regulation of cerebellar 5-HT(2C) receptors in pilocarpine-induced epilepsy in rats: therapeutic role of Bacopa monnieri extract

• Published in: Journal of the neurological sciences Vol. 284; no. 1-2; p. 124
• Main Authors: Krishnakumar, Amee, Abraham, Pretty Mary, Paul, Jes, Paulose, C S
• Format: Journal Article
• Language: English
• Published: Netherlands 15.09.2009
• Subjects: Animals; Anticonvulsants - isolation & purification; Anticonvulsants - pharmacology; Anticonvulsants - therapeutic use; Ataxia - drug therapy; Ataxia - etiology; Bacopa - chemistry; Carbamazepine - pharmacology; Carbamazepine - therapeutic use; Cerebellum - drug effects; Cerebellum - metabolism; Down-Regulation - drug effects; Drug Evaluation, Preclinical; Epilepsy - chemically induced; Epilepsy - drug therapy; Epilepsy - genetics; Epilepsy - metabolism; Male; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Phytotherapy; Pilocarpine - toxicity; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Protein Binding - drug effects; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2C - genetics; Receptor, Serotonin, 5-HT2C - metabolism; Serotonin - metabolism; Serotonin Receptor Agonists - isolation & purification; Serotonin Receptor Agonists - pharmacology; Serotonin Receptor Agonists - therapeutic use
• ISSN: 1878-5883
• DOI: 10.1016/j.jns.2009.04.032

Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory action on cerebellar function through 5HT(2C) receptors. 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs. In the present study, we investigated the changes in the 5-HT(2C) receptors binding and gene expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a significant down regulation of the 5-HT content (p<0.001), 5-HT(2C) gene expression (p<0.001) and 5-HT(2C) receptor binding (p<0.001) with an increased affinity (p<0.001). Carbamazepine and B. monnieri treatments to epileptic rats reversed the down regulated 5-HT content (p<0.01), 5-HT(2C) receptor binding (p<0.001) and gene expression (p<0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the upregulation of 5-HT(2C) receptor in epileptic rats. This has clinical significance in the management of epilepsy.