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 Table of Contents    
Year : 2013  |  Volume : 45  |  Issue : 5  |  Page : 537-538

Exploring selective serotonergic modulation involved in the anticonvulsant effect of Ficus religiosa fig extract

Department of Pharmaceutical Sciences and Drug Research, Punjab University, Patiala, Punjab, India

Date of Web Publication6-Sep-2013

Correspondence Address:
Rajesh Kumar Goel
Department of Pharmaceutical Sciences and Drug Research, Punjab University, Patiala, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.117768

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How to cite this article:
Goel RK, Singh D. Exploring selective serotonergic modulation involved in the anticonvulsant effect of Ficus religiosa fig extract. Indian J Pharmacol 2013;45:537-8

How to cite this URL:
Goel RK, Singh D. Exploring selective serotonergic modulation involved in the anticonvulsant effect of Ficus religiosa fig extract. Indian J Pharmacol [serial online] 2013 [cited 2023 Feb 2];45:537-8. Available from: https://www.ijp-online.com/text.asp?2013/45/5/537/117768


In our previous study, methanol fig (fruit) extract of Ficus religiosa showed a dose-dependent anticonvulsant effect against maximal electroshock (MES)- and Picrotoxin-induced convulsions in mice. The extract was found to be safe at 10 times of its effective doses, and was devoid of neurotoxic effects, as shown by conventional antiepileptic drugs. The anticonvulsant effect of the extract was abolished by pre-treatment with cyproheptadine (a non-selective 5-HT 1/2 receptor blocker). The study showed that the extract may act through modulation of 5-HT 1/2 receptor subtype functions. [1] The role of several serotonin receptor subtypes have been indicated in epilepsy. Among all, 5-HT 1A , 5-HT 2A , 5-HT 2C , 5-HT 3 and 5-HT 7 receptors are known to play a crucial role in the pathogenesis of epilepsy. These receptors are widely located on cortical and/or hippocampal glutamatergic or gamma-aminobutyric acid (GABA)ergic neurons or terminals, where activation of these receptors by serotonin causes modulation of glutamatergic and/or GABAergic functions, which are solely involved in the pathogenesis of epilepsy, or change ionic conductance and/or concentration within the cells, resulting in de-or hyper-polarization of neurons. Broadly, agonism at 5-HT 1A , 5-HT 2A and 5-HT 2C receptors and antagonism of 5-HT 3 and 5-HT 7 results in inhibition of abnormal neuronal excitation, leading to anticonvulsant effect. [2],[3],[4] Since the fig extract contained serotonergic component and its effect was abolished by a non-selective 5-HT 1/2 blocker, [1] indicating its agonistic effect responsible for the activity. Therefore to find out the specific serotonergic agonism of the extract, its effect after pre-treatment with 5-HT 1A , 5-HT 2A and 5-HT 2C receptor blockers was studied.

The experimental protocol was approved by the Institutional Animal Ethical Committee established by the University. Male Swiss albino mice weighing 20-30 g were divided into eight different groups (n = 6) for MES test. First group served as control and received 10 mL/kg; i.p. vehicle (9:1; distilled water: Dimethyl sulfoxide). Second group received Phenytoin (25 mg/kg; i.p.) and served as reference standard. Three groups were injected with 25, 50 and 100 mg/kg, i.p. doses of methanol fig extract of Ficus religiosa (prepared and characterized as described in our previous study). [1] Remaining three groups were injected with WAY-100635 (1 mg/kg; i.p.) or Clozapine (10 mg/kg; i.p.) or Olanzapine (3 mg/kg; i.p.), 30 min prior to the dosing of the extract (100 mg/kg; i.p.). After 30 min, all the animals received a calibrated (through a current calibrator) transauricular electroshock of 56 mA for 0.2 s using a convulsiometer (Rolex, Ambala, India). The duration of tonic hind limb extension (seconds) was noted. Similarly in Picrotoxin test, the animals were divided into different groups and were initially given the same treatment as that of MES test, but in this case instead of Phenytoin, Diazepam (5 mg/kg; i.p.) served as the reference standard. In this test, convulsions were induced by injecting Picrotoxin (5 mg/kg, i.p.), 30 min after above mentioned treatments. The latency to clonic convulsions (min) was noted. In all cases, 30 min were given upper cutoff time. All the results were expressed as mean ± standard error of the mean. Data was analyzed using the one-way analysis of variance followed by Tukey's test. The results were regarded as significant at P < 0.05.

Treatment with the extract (25, 50 and 100 mg/kg) significantly (P < 0.001) decreased the duration of tonic hind limb extension in MES test (F (7,40) = 22.585, P < 0.001) and increased the latency to clonic convulsions in Picrotoxin test (F (7,40) = 133.575, P < 0.001) as compared with the vehicle control, showing maximum protection at 100 mg/kg dose. These results are in line with the results of our previous study. [1] In both tests, treatment with Clozapine (5-HT 2C > 2A blocker) and Olanzapine (5-HT 2A > 2C blocker) showed no change in the anticonvulsant effect of the extract as compared with 100 mg/kg per se extract treated group, whereas WAY-100635 (5-HT 1A blocker) pre-treatment abolished its protective effect [Table 1].
Table 1: Effect of various pharmacological interventions on MES-and Picrotoxin-induced convulsions

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Serotonin receptor subtypes, 5-HT 2A and 5-HT 2C are widely expressed throughout the central nervous system and their activation by endogenous serotonin results in the release of GABA through several signaling mechanisms resulting in increased central inhibitory tone. [2],[3],[5] Whereas, 5-HT 1A receptors are expressed significantly in serotonin containing neurons in the raphe nuclei, cholinergic neurons in the septum and glutamatergic neurons in the cortex and hippocampus. Activation of 5-HT 1A receptor causes membrane hyperpolarization associated with increased potassium conductance. Moreover, these receptors also inhibit Mg 2+ -induced epileptiform activity, through the reduction of N-methyl-D-aspartate-mediated excitatory postsynaptic potential in different regions of the hippocampus. [2],[4] The abolition of anticonvulsant effect by WAY-100635, which is a selective 5-HT 1A receptor antagonist, and not by Clozapine and Olanzapine suggests the role of 5-HT 1A agonism for the anticonvulsant effect of the extract. Therefore, it can be concluded that Ficus religiosa fig extract shows its anticonvulsant effect by selective 5-HT 1A agonism.

 » Acknowledgments Top

The authors are deeply grateful to the University Grant Commission, New Delhi, India, for providing financial assistance (Vide F. No.: 34-130/2008 [SR]) for the project and project fellowship to Mr. Damanpreet Singh. The authors are also thankful to Parasol Laboratories Pvt. Ltd., (Baddi, India) for providing gift samples of Clozapine and Olanzapine.

 » References Top

1.Singh D, Goel RK. Anticonvulsant effect of Ficus religiosa: Role of serotonergic pathways. J Ethnopharmacol 2009;123:330-4.  Back to cited text no. 1
2.Bagdy G, Kecskemeti V, Riba P, Jakus R. Serotonin and epilepsy. J Neurochem 2007;100:857-73.  Back to cited text no. 2
3.Theile JW, Morikawa H, Gonzales RA, Morrisett RA. Role of 5-hydroxytryptamine2C receptors in Ca 2+ -dependent ethanol potentiation of GABA release onto ventral tegmental area dopamine neurons. J Pharmacol Exp Ther 2009;329:625-33.  Back to cited text no. 3
4.Theodore WH. Does serotonin play a role in epilepsy? Epilepsy Curr 2003;3:173-7.  Back to cited text no. 4
5.Fink KB, Göthert M. 5-HT receptor regulation of neurotransmitter release. Pharmacol Rev 2007;59:360-417.  Back to cited text no. 5


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