Anxiety and Hyperlocomotion Induced by Chronic Unpredictable Mild Stress Can Be Moderated with Melatonin Treatment

Abstract

Preclinical studies have shown that melatonin exercised antidepressant-like and anxiolyticlike effects in animal models of anxiety. The aim of the present study was to correlate the changes in behaviour induced by melatonin treatment with the activity of the dopaminergic system in the hippocampus of Wistar rats exposed to chronic, unpredictable, mild stress (CUMS). Male Wistar rats, 11 weeks old, were subjected to chronic stress for 28 successive days. Separate groups of control and stressed rats were intraperitoneally injected daily either with melatonin (10 mg/kg/day, i.p.) or placebo (5% ethanol). The open-field and elevated plus-maze tests were used to assess locomotor activities and anxiety levels. The content of dopamine (DA) in the hippocampal tissues was determined using radioenzymatic assay, while changes in tyrosine hydroxylase (TH) mRNA and protein levels in the hippocampus were determined using real-time RT-PCR and Western immunoblotting. Chronic stress led to reduction in the hippocampal dopaminergic content without affecting the levels of TH protein. These changes were accompanied by increased locomotor activity and higher anxiety levels in the open-field test. Administration of melatonin for 28 days resulted in an increase in the hippocampal DA content as a result of elevated TH protein levels. Melatonin showed an improvement in anxiety-like behaviour along with significantly reduced exploration. We could conclude that melatonin may stimulate dopaminergic synthesis in the hippocampus in order to suppress stress-induced behaviour.