Abstract
Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric (p.o.) combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice.
Highlights
The efficacy of current antidepressant therapy is not satisfactory, resulting in the introduction of poly/adjunctive agents to enhance the activity of classical agents in the treatment of depression.Recently, Nowak et al (2003) [1] demonstrated the potency of zinc (Zn) as an adjunct to tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in the treatment of unipolar depression
Different dose regimens of Zn + IMI treatment are active in the forced swim test (FST) in mice and rats following intraperitoneal (i.p.)
The animals were housed in environmentally controlled rooms with a 12 h day/night cycle, in standard cages under strictly controlled laboratory conditions
Summary
The efficacy of current antidepressant therapy is not satisfactory, resulting in the introduction of poly/adjunctive agents to enhance the activity of classical agents in the treatment of depression. Nowak et al (2003) [1] demonstrated the potency of zinc (Zn) as an adjunct to tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) in the treatment of unipolar depression. Confirmed the beneficial effects of Zn supplementation in conjunction with SSRI antidepressant drugs. Preclinical studies have demonstrated the antidepressant-like activity of Zn as well as the enhancement of antidepressant efficacy after co-treatment with Zn and antidepressant drugs in various tests and models of depression [5,6]. Much research has been devoted to study the effects of the joint administration of Zn + IMI in animal models of depression. Different dose regimens of Zn + IMI treatment are active in the FST in mice and rats following intraperitoneal (i.p.)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
