HISTOLOGICAL AND IMMUNOHISTOCHEMICAL IMPLICATIONS OF KETAMINE PROTRACTED DOSES AS A NOVEL CANDIDATE IN ANTIDEPRESSANT TREATMENTON ADULT RAT CEREBELLAR CORTEX.

Background:- Ketamine is commonly used as a dissociative anesthetic drug. However, some clinical studies suggested that ketamine ameliorated depressive symptoms in patients with major depression. Therefore, this study aimed to investigate histological and immunohistochemical implications of variable doses of ketamine administration on adult rat cerebellar cortex. Material/Methods:- Thirty adult rats were divided into; group I (control), group II received IP injection of 5 mg/kg ketamine / 12 hours, and group III received IP injection of 20 mg/kg ketamine / 12 hours. After 14 days, cerebella were taken and prepared for histological study and immunohistochemical study for glial fibrillary acidic protein (GFAP) as a biomarker of neurotoxicity and for calretinin that plays an important role in the regulatory processes of calcium and has an anti-apoptotic cellular protective action. Results:- Compared to group I, group II showed minimal degenerative changes. Purkinje cell layer showed a significant decrease in GFAP immune- reaction and a significant increase in calretinin immune- reaction. Molecular and granular layers showed insignificant increase in GFAP immune- reaction and insignificant decrease in calretinin immune- reaction. Group III showed massive degenerative changes in the cerebellar cortex in addition to a significant decreased in GFAP and a significant increase in calretinin immune-reaction in Purkinje cell layer. Molecular and granular layers showed a significant increase in GFAP and a significant decrease in calretinin immune- reaction. Conclusion:- repeated administration of ketamine induced dose dependent structural and immunohistochemical alterations in the cerebellar cortex, suggesting that the use of small doses is much safer.