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The Neurochemical Effects of Harmine in Animal Models of Depression

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Harmine is a β-carboline that acts on the CNS, by inhibiting the enzyme monoamine oxidase type A-MAO. This alkaloid binds with affinity to receptors on serotonin as 5-hydroxytryptamine, 5-HT2C subtypes and 5-HT2A receptors and imidazole (I2). The objective of this study was to investigate the physiological and behavioral effects of acute and chronic administration of harmine (5, 10 and 15 mg / kg) and imipramine (10, 20 and 30 mg / kg) using the forced swimming test (TNF) and the protocol of chronic mild stress (ECM) in an animal model. The results showed that rats treated acutely and chronically with harmine and imipramine reduced the immobility time in the TNF, and increased both climbigns and swimming time of rats compared to saline group, without affecting locomotor activity in the open field test. Both acute and chronic administration of harmine increased factor brain-derived neurotrophic (BDNF) protein levels in the rat hippocampus. Our findings demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, increase ACTH circulating levels in rats and increase BDNF protein levels. Interestingly, treatment with harmine for 7 consecutive days, reversed anhedonia, the increase of adrenal gland weight, normalized ACTH circulating levels and BDNF protein levels. Finally, these findings further support the hypothesis that harmine could be a new pharmacological tool for the treatment of depression.

Fortunato, J. J. 2009. The Neurochemical Effects of Harmine in Animal Models of Depression. PhD thesis.
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