DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20175689

Fluoxetine enhances maximal electroshock seizure threshold in Albino rat model when compared to phenytoin

Tanmoy Gangopadhyay, Ananya Mandal, Uma Shanker Keshri

Abstract


Background: Individuals with epilepsy have a higher incidence of psychiatric disorders than person without epilepsy. Epidemiological studies have shown that the co-morbidity of epilepsy and depression to be high as 50%. The conventional anti-depressants are believed to lower the seizure threshold making it difficult to treat the co-morbid depression, but animal studies have shown SSRIs, a common anti-depressant, to have anti-convulsant properties. So, we propose to study the anticonvulsant effects of fluoxetine, a SSRI, in albino rats against maximal electroshock seizure and to compare against a standard antiepileptic drug phenytoin.

Methods: The anticonvulsant effect of fluoxetine was observed in model of maximal electroconvulsive seizure threshold in albino rats. The animals were divided into 3 groups having 6 animals each, receiving distilled water, fluoxetine and phenytoin respectively. The drugs were given orally, and the effect was observed on day 7, 14 and 21. Tonic hind-limb extension was taken as the parameter of electroshock seizure. The effects were compared against a standard anti-seizure drug phenytoin.

Results: Fluoxetine showed significant elevation of the seizure threshold following 14 days of administration (P value 0.031). The effect was comparable to phenytoin with no significant difference after 7, 14 and 21 days of treatment (P-value 0.485, 0.699 and 0.818 respectively) though phenytoin showed significant anti-seizure effect since day 7 of treatment.

Conclusions: Fluoxetine showed significant anti-seizure activity against electroconvulsive seizure in albino rats.


Keywords


Anticonvulsant, Albino rats, Fluoxetine, Maximal electroshock seizure, Phenytoin

Full Text:

PDF

References


Ebert U. Basic mechanism of psychotropic drugs. Epilepsia. 2002;43:2-7.

Gross R, Dannon P, Lepkifker E, Zohar J, Kotler M. Generalized seizures caused by fluoxetine overdose. Am J Emerg Med. 1998;3:328-30.

Skowron DM, Stimmel GL. Antidepressants and the risk of seizures. Pharmacoth. 1992;12:18-22.

Jobe PC, Browning RA. The serotonergic and noradrenergic effects of antidepressant drugs are anticonvulsant, not proconvulsant. Epilepsy Behav. 2005;7:602-19.

Bagdy G, Kecskemeti V, Riba P, Jakus R. Serotonin and epilepsy. J Neurochem. 2007;100:857-73.

Bonnycastle DD, Giarman NJ and Paasonen MK. Anticonvulsant compounds and 5-hydroxytryptamine in rat brain. Br J Pharmacol. 1957;12:228-31.

Browning RA, Wood AV, Merrill MA, Dailey JW, Jobe PC. Enhancement of the anticonvulsant effect of fluoxetinefollowing blockade of 5-HT1A receptors. Eur. J. Pharmacol 1997;336:1-6.

Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacol. 1998;38:1083-152.

Hesdorffer DC, Hauser WA, Annegers JF, Cascino G. Major depression is a risk factor for seizures in older adults. Ann Neurol. 2000;47:246-9.

Nemeroff CB, Owens MJ. Treatment of mood disorders. Nat Neurosci. 2002;5:1068-70.

Behr J, Heinemann U. Effects of serotonin on different patterns of low Mg2+-induced epileptiform activity in the subiculum of rats studied in vitro. Brain Res. 1996;737:331-4.

Schmitz D, Empson RM, Gloveli T, Heinemann U. Serotonin blocks different patterns of low Mg2+-induced epileptiform activity in rat entorhinal cortex, but not hippocampus. Neurosci. 1997;76:449-58.

Marwah R, Pal SN, Pillai KK. Effect of fluoxetine on increasing-current electrochock seizures (ICES) in mice. Indian J Pharmacol. 1999;31:350-3.

Borowicz KK, Stepień K, Czuczwar SJ. Fluoxetine enhances the anticonvulsant effects of conventional antiepileptic drugs in maximal electroshock seizures in mice. Pharmacol Rep. 2006;58:83-90.

Peričić D, Lazić J, Jembrek J, Maja SS. Stimulation of 5-HT1A receptors increases the seizure threshold for picrotoxin in mice. Eur J Pharmacol. 2005;527:105-10.

Yan QS, Jobe PC, Cheong JH, Ko KH, Dailey JW. Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats. Arch Pharmacol. 1994;350(2):149-52.

Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, et al. Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors. Nat. 1995;374:542-6.

Brennan TJ, Seeley WW, Kilgard M, Schreiner CE, Tecott LH. Sound-induced seizures in serotonin 5-HT2C receptor mutant mice. Nat Genet. 1997;16:387-90.

Applegate CD, Tecott LH. Global increases in seizure susceptibility in mice lacking 5-HT2C receptors: a behavioral analysis. Exp Neurol. 1998;154:522-30.

Favale E, Rubino V, Mainardi P, Lunardi G, Albano C. Anticonvulsant effect of fluoxetine in humans Neurol. 1995;45:1926-7.