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Effects of Chronic Ketamine Exposure on Habenula Nucleus: A Histomorphometric and Stereological Study

Abstract

Introduction: Ketamine is an anesthetic drug that has been recently used in the treatment of mood disorders. The aim of this study was to examine the effects of chronic use of ketamine on the neuroglial elements of Habenula nucleus.

Materials and methods: Male wistar rats (8 weeks old) (200 ± 20 gr) were divided into 2 groups (N=10) namely experimental and control. Experimental group received ketamine at dose of 10 mg/kg intraperitoneally for one week. The control animals were treated with saline. The brains were processed and stained with H and E. The bilateral surface of the HB were defined and measured with software. The number of astrocytes and dark neurons were counted on both sides according to the modified stereology method.

Results: The number of dark neurons in the medial Habenula HB of experimental group (15 ± 4) that showed significant difference in comparison with those of control. The wet weight of the adrenal gland in the experimental group (42.5 ± 7 mg) showed significant level of difference in comparison with those of control (18 ± 1.20 mg) (P<0.05). The weight of wet brain (the brain stem and cerebrum were removed) in ketamine group (1.28 ± 0.04 gr) showed meaningful difference in comparison with control (1.71 ± 2 gr) (P<0.05). Histomorphometry of the HB in the experimental animals showed no meaningful difference with those of the control animals (p>0.05). The number of counted astrocytes in experimental group showed significant difference in comparison to those of the control group (P<0.05).

Conclusion: The results of this study revealed that chronic exposure to ketamine is not associated with histomorphometric changes in the HB. Furthermore, our results showed that chronic use of ketamine leads to reactive gliosis and neuronal death in the medial HB. The ketamine induced neurodegeneration was associated with decreased brain weight and adrenal hypertrophy.

Divya Sharma

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