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- Title
Behavioral and histopathological validation of ketamine-induced schizophrenia.
- Authors
Tekin, Nurdan; Karamahmutoğlu, Tuğba; Idrizoğlu, Medine Gülçebi; Bangır, Dilek; Gören, Mehmet Zafer
- Abstract
Objective: Schizophrenia is a one of the most devastating and complex psychiatric disorder. Due to this complexity, its difficult to find adequate animal models. It has been known that Damphetamine, phencyclidine, ketamine can induce strong psychotic effects both in human and rodents. In this study, we aimed to validate the behavioral and histopathological alterations in the subchronic ketamine-induced rat schizophrenia. Methods: We administered a sub-anesthetic dose of ketamine (25 mg/kg, i.p.) daily for eight consecutive days to adult male Wistar rats (n=8). The animals in the ketamine group received acute intraperitoneal injections of either chlorpromazine (1 mg/kg) or saline on test days. On the 7th and 8th days, the behavioral tests were evaluated. Behaviors related to the positive (locomotor activity), negative (social interaction) and cognitive (novel object recognition) symptoms were assessed. The tyrosine hydroxylase (TH) staining was implemented to observe dopaminergic neurons in the striatum. Results: The results of locomotor activity test demonstrated that admistiration of ketamine significantly increased the total distance traveled (3626±350.6 vs 2176±169.8, p<0.01) and the percentage of stereotypic behavior (11.07±0.917 vs 7.14±0.63, p<0.05), as compared to saline controls. Also acute chlorpromazine injection decreased the hyperlocomotion (2381±220.4 vs 3626±350.6, p<0.05) and stereotypy (7.769±0.49 vs 11.07± 0.91, p<0.05) as compare to ketamine-induced group. As compared to saline control, ketamine significantly decreased social interaction time (331±24.7 vs 171.1±22.2, p<0.0001) and chlorpromazine did not reversed this social deficit. Also ketamine impaired the object recognition (0.457±0.02 vs 0.677±0.03, p<0.002) as compared to sal controls and chlorpromazine did not reversed the deficit. Histopathological evaluation showed that the density of TH immunoreactivity in the ketamineadministered rats was increased in the striatum compared to controls (p<0.001). Conclusion: The results of this study imply that subchronic administration of ketamine can induce schizophrenia-like alterations in rats and therefore this animal model may be beneficial in the research of schizophrenia.
- Subjects
TYROSINE hydroxylase; SCHIZOPHRENIA; DOPAMINERGIC neurons; PHENCYCLIDINE; INTRAPERITONEAL injections
- Publication
Anatomy: International Journal of Experimental & Clinical Anatomy, 2019, Vol 13, Issue S1, pS59
- ISSN
1307-8798
- Publication type
Article