Effects of topiramate pretreatment on ketamine induced behaviors in rats

D.V. Gokhale, T.R.Patil,. Mrs.C.C. Khanwelkar,. R.P.Limaye,. Mrs.Neeta A. Grover and Pendhari S

Topiramate has been used as an add-on-drug with typical antipsychotics to treat negative and cognitive symptoms of schizophrenia. The present study investigated if topiramate exhibits atypical antipsychotic-like activity, has any potential to precipitate or exacerbate psychosis and its ability to relieve negative symptoms of schizophrenia.

Aims: To study the effects of topiramate pretreatment on ketamine induced behavioral effects in the rats.

Methods: Hyperlocomotion and stereotyped behaviors were induced in the rats by acute administration of ketamine (25mg./kg. i.p.). Ketamine in low dose (2mg./kg. i.p.) produced social isolation and deficits in the social interaction in the rats. The effect of topiramate (40mg./kg and 80mg./kg. p.o.) pretreatment on hyperlocomotion was evaluated by activity scores measured with automated actophotometer and stereotyped behavior was graded by trained observers. The effect of topiramate pretreatment on ketamine induced deficits in the social interaction in the rats was evaluated by manually performed social interaction test.

Data analysis: Locomotor activity and social interaction scores were analysed by two tailed, unpaired student’s ‘t’ - test. Stereotyped Behaviors’ highest scores, were evaluated by Mann Whitney U test. Value of p<0.05 was considered statistically significant.

Results: Topiramate decreased ketamine induced hyperlocomotion and stereotyped behavior in the rats which was statistically not significant. Topiramate significantly reduced ketamine induced social isolation in the rats.
Conclusion: Topiramate did not exhibit either atypical antipsychotic-like activity or the potential to precipitate/exacerbate psychosis. Topiramate could be effective in relieving negative symptoms of schizophrenia and it appears that topiramate has the potential to improve negative affective states..

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DOI: http://dx.doi.org/10.24327/23956429.ijcmpr20170130