In this study the long-term effects of morphine sulphate treatment (MST) on histopathological and biochemical changes in the cerebellum was assessed in albino rats. Normal saline (5ml) was given orally as placebo in the control group (n=25). Morphine groups received morphine orally at a dose level of 5mg/kg body weight day after day for 10, 20 and 30 days (n=25/group). Light microscopy revealed that the molecular layer showed vacuolation. The Purkinje cells lost their specific shaped appearance, decreased in size and numbers. The granular cells highly degenerated. Electron microscopy revealed fragmentation of the cisterns of the both types of endoplasmic reticulum, resulted in a progressive depletion of total protein contents as well as general carbohydrates in all treated groups as supported by histochemical observation. Obvious destruction of mitochondrial inner membrane and cristae mediate cell death. Also, abnormal nucleus with deformed perforated nuclear membrane and deformation of the plasma membrane with degeneration of the synapses could interpreted as a sign of necrosis. Biochemical analysis revealed that dopamine (DA) and norepinephrine (NE) were significantly decreased in four brain areas (cortex striatum, thalamus/hypothalamus, and cerebellum). In contrast, serotonin (5-HT) level was increased in these brain regions; with an exception of 5-HT on day 10 and neurotransmitter levels in the pons were unaffected. The quantitative analysis showed a significant decrease (P<0.05) in the diameter of Purkinje cells and in the thickness of both molecular and granular layers treated groups. Morphine sulphate induces may be a cell death or necrosis in the rat cerebellum and modulating neurotransmitter system. Our findings pointed out the risk of increased cerebellum damage due to long-term of morphine use.
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