Magnesium is one of the most essential mineral in the human body, connected with brain biochemistry and the fluidity of neuronal membrane. A variety of neuromuscular and psychiatric symptoms, including different types of depression, was observed in magnesium deficiency. Plasma/serum magnesium levels do not seem to be the appropriate indicators of depressive disorders, since ambiguous outcomes, depending on the study, were obtained. The emergence of a new approach to magnesium compounds in medical practice has been seen. Apart from being administered as components of dietary supplements, they are also perceived as the effective agents in treatment of migraine, alcoholism, asthma, heart diseases, arrhythmias, renal calcium stones, premenstrual tension syndrome etc. Magnesium preparations have an essential place in homeopathy as a remedy for a range of mental health problems. Mechanisms of antidepressant action of magnesium are not fully understood yet. Most probably, magnesium influences several systems associated with development of depression. The first information on the beneficial effect of magnesium sulfate given hypodermically to patients with agitated depression was published almost 100 years ago. Numerous pre-clinical and clinical studies confirmed the initial observations as well as demonstrated the beneficial safety profile of magnesium supplementation. Thus, magnesium preparations seem to be a valuable addition to the pharmacological armamentarium for management of depression.
Zinc exhibits antidepressant-like activity in preclinical tests (the forced swim test and tail suspension test) and in olfactory bulbectomy and chronic unpredictable stress; two models of depression. Zinc also enhances the treatment of depression in humans. In the present study we evaluated the antidepressant activity of zinc in another model of depression-chronic mild stress (CMS) and the effect of zinc treatment on BDNF protein and the mRNA level. In CMS zinc hydroaspartate (10 mg/kg) exhibited a rapid (after 1 week of treatment) antidepressant-like effect. Chronic treatment with zinc induced a 17-39% increase in the BDNF mRNA and protein level in the hippocampus. These data indicate a rapidly acting antidepressant-like activity of zinc in CMS and the involvement of zinc in the regulation of BDNF.
Caffeine is the most widely used behaviorally active drug in the world which exerts its activity on central nervous system through adenosine receptors. Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. The main goal of the present study was to evaluate the influence of caffeine on animals’ behavior in forced swim test (FST) as well as the effect of caffeine (5 mg/kg) on the activity of six typical antidepressants, such as imipramine (15 mg/kg), desipramine (10 mg/kg), fluoxetine (5 mg/kg), paroxetine (0.5 mg/kg), escitalopram (2 mg/kg), and reboxetine (2.5 mg/kg). Locomotor activity was estimated to verify and exclude false-positive/negative results. In order to assess the influence of caffeine on the levels of antidepressant drugs studied, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. The results showed that caffeine at a dose of 10, 20, and 50 mg/kg exhibited antidepressant activity in the FST, and it was not related to changes in locomotor activity in the animals. Caffeine at a dose of 5 mg/kg potentiated the activity of all antidepressants, and the observed effects were not due to the increase in locomotor activity in the animals. The interactions between caffeine and desipramine, fluoxetine, escitalopram, and reboxetine were exclusively of pharmacodynamic character, because caffeine did not cause any changes in the concentrations of these drugs neither in blood serum nor in brain tissue. As a result of joint administration of caffeine and paroxetine, an increase in the antidepressant drug concentrations in serum was observed. No such change was noticed in the brain tissue. A decrease in the antidepressant drug concentrations in brain was observed in the case of imipramine administered together with caffeine. Therefore, it can be assumed that the interactions caffeine-paroxetine and caffeine-imipramine occur at least in part in the pharmacokinetic phase.
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