Vitamin D3 and zinc supplements augment the antimanic efficacy of lithium and olanzapine treatments in an animal model of mania.

Objective: Bipolar disorder (BD) is a challenging psychiatric disorder and a complex disease. The associated reduction in serum vitamin D3 (VitD3) levels in BD patients and the contribution of zinc (Zn) to the treatment, along with the severe side effects of lithium (Li) treatment, were encouraging to assess the efficacy of different correlated combinations of therapeutic/nutraceutical treatments such as olanzapine (Oln), VitD3, and Zn against Li. Methods: Mania was induced in C57BL/6 mice by administering methylphenidate (MPH) for 14 consecutive days. On the 8th day of MPH injection, different treatment regimens were administered, Li, Oln, VitD3/Zn, VitD3/Zn/Oln, VitD3 + Zn + Oln + Li50mg/kg (C50), and VitD3 + Zn + Oln + Li100mg/kg (C100). Both VitD3 (850 IU/kg) and Zn (180 mg/kg) were supplied with food for 2 weeks before starting the induction of mania, which continued until the end of MPH administration. Behavioral, brain oxidative stress, thyroid hormones, VitD3, Zn, GsK-3ß, and Bcl2 levels, as well as brain histopathological alterations, were assessed. Results: Manic mice exhibited alterations in all tested parameters, and the histopathological examination of the cortex and hippocampus confirmed these results. The VitD3/Zn/Oln, C50, and C100 treatment regimens reversed most of the behavioral and pathophysiological alterations; however, the C50 treatment regimen was the most efficient. Conclusions: This study emphasizes the importance of combining different antimanic medications like Li and Oln with nutraceutical supplements to increase their antimanic efficacy, reduce their adverse effects, and, ideally, improve the BD patient's quality of life.

Effects of Chronic Caffeine Administration on Behavioral and Molecular Adaptations to Sensory Contact Model Induced Stress in Adolescent Male Mice.

Previous studies have shown that caffeine attenuates stress-induced mood dysfunction and memory deterioration through neuronal adenosine A2A receptors antagonism. However, whether caffeine exerts this effect through modulating other molecular targets, which interfere with the resilience to social defeat stress in adolescent male mice is unknown. This study was conducted to investigate the role of caffeine in the behavioral responses to social stress induced by the sensory contact model (SCM) and the possible alteration of the gene expression level of Na/K ATPase pump. Adolescent male mice were exposed to SCM for 12 days. Caffeine was administered intraperitoneal daily for 14 days after SCM. The time spent in interaction zone, social interaction ratio, preference index to novel objects, time spent in the open arms and immobility time in forced swimming test were used to measure the locomotor activity, social avoidance, short-term memory, anxiety and depression in mice. The results showed that chronic treatment with caffeine for 14 days improved locomotor activity, reversed the avoidance of social behavior, improved preference to novel objects, and reversed depression induced by social defeat stress in adolescent male mice, suggesting the enhancement of the resilience to social defeat stress induced by caffeine. Moreover, caffeine treatment did alter gene expression levels of Na/K ATPase isoforms in both prefrontal cortex and hippocampus. Altered gene expression was significant in most cases and correlates with the observed behavioral changes. Taken together, our findings provide new insight into the effects of chronic caffeine administration on locomotor activity, social avoidance, short-term memory and depression in adolescent male mice exposed to SCM.

Bridge to recovery: what remains to be discovered?

The use of left ventricular assist devices to induce substantial myocardial recovery with explantation of the device, bridge to recovery (BTR), is an exciting but currently grossly underused application. Recently acquired knowledge relating to BTR and its mechanisms offers unprecedented opportunities to streamline its use and unravel some of the secrets of heart failure with much wider implications. This article reviews the status, challenges, and future of cardiac recovery.