Abstract
Despite progressive improvement in treating major depressive disorder (MDD), it remains mostly unresponsive to one antidepressant medication. Zinc is a brain highly abundant trace metal, a brain derived neurotrophic factor (BDNF) inducer, a modulator of synaptic plasticity and potent suppressor of the NMDA receptors. We proposed that co-administration of zinc with the antide-pressants may represent a valuable regimen to improve the efficacy of these drugs. This work has been implemented to evaluate the behavioral changes of acute and sub-acute co-administration of zinc with Paroxtine in mice. Methods: The animals were injected intra-peritoneal with either Paroxtine (20 mg/kg) which was a selective serotonin reuptake inhibitor (SSRI), zinc sulfate (30 mg/kg) or Paroxtine in combination with zinc for one day and one week (once daily). The pattern of the animal behavior was assessed in the forced swim test (FST). Results and Discussion: The behavioral patterns of the animals in the FST include immobility, swimming and climbing. Successful antidepressant should decrease the immobility time with either increase in swimming and/or climbing behavior based on the drug pharmacological activity. Our results revealed a significant decrease of immobility and increase of swimming behavior indicating serotonin-dependent pharmacological activity of Paroxtine or zinc alone as well as in the animals treated with zinc in combination with Paroxtine. There was no significant difference in the animals’ behavior between acute and sub-acute treatment with zinc or even upon its addition to paroxetine. Our data support the concept that co-administration of zinc may provide further antidepressant activity. Zinc may offer additional clinical value particularly in geriatric patients or other populations where zinc level has shown dramatic decrease.
Highlights
Major depression disorder (MDD) is responsible for high morbidity in the overall population
The dose of 30 mg/kg was chosen for use in the studies of interaction of antidepressants with zinc
On the other hand, combined administration of zinc with Prx had no effect on the locomotor activity in mice Figure 3
Summary
Major depression disorder (MDD) is responsible for high morbidity in the overall population. It is an overwhelming illness that affects 17% of the population at some point in life, resulting in major social and economic consequences [1]. It is a chronic disorder, commonly characterized by relapses and recurrences. The efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity. Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects [5]. From 10% - 30% of depressed patients taking antidepressants are partially or totally resistant to the treatment [6] [7] and recurrence of depression while still taking medication can occur [8]
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