Marwa Mostafa Awad, Omayma Anwar Khorshid, Magdy Ishak Attallah, Laila A. Rashed, Hedayet Mahmoud Tolba

Abstract

Subclinical hypothyroidism is becoming a global health problem due to its increasing prevalence and potentially deleterious effects on cognitive, mood memory, and other higher brain functions. Recently, an important concern is the inefficiency of levothyroxine for depressive symptoms in patients with SCH. The aim of this work was to compare the possible effects of three different antidepressant drugs; Milnacipran as a standard antidepressant, Agomelatine, another antidepressant acting via melatonin receptors, and Hypericum perforatum, the proven antidepressant, on the depression-like behavior performances, the serum level of cortisol, serum level of TNFα, the level of monoamines and Brain-Derived Neurotrophic Factor (BDNF) in the hippocampus in an experimentally–induced model of SCH in rats. 60 adult male rats were chosen and divided into 6 groups. The rats with SCH were induced by hemi-thyroid electrocauterization in 4 groups: model group, Milnacipran-treated group (10 mg/kg/day), Agomelatine-treated-group (40 mg/Kg/day), and H. Perforatum treated-group (200 mg/kg/day). The treatment duration was 2 weeks. The depressive-like behavior was assessed by OFT and FST. The biochemical assessment involved the hippocampal monoamines and BDNF, TNF alpha, and cortisol levels in serum at the end of the study. Milnacipran, Agomelatine, and H. Perforatum treatment alleviated the behavioral performance changes and decreased the elevated serum cortisol and TNF alpha. Also, the drugs used increased the Hippocampal monoamines and BDNF levels in the SCH rats. Comparing the three tested drugs, the results of the H. Perforatum treatment were comparable to that of Milnacipran and superior to Agomelatine results in most of the tested parameters. Treatment with H. Perforatum extract resulted in marked improvement of behavioral and biochemical changes in the SCH model group, which was in a comparable manner to the standard antidepressant drug Milnacipran. Also, an improvement was observed with Agomelatine but it was lesser than that of Milnacipran and H. Perforatum extract.