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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.

Administration of Zinc with Paroxetine Improved the Forced Swim Test Behavioral Pattern of Treated Mice in Acute and Sub-Acute Study