ABSTRACT
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.
ABSTRACT
Being a critical neurodevelopmental stage that is affected by social conditions, the period of adolescence was chosen as the age of examining possible modification of alcohol neurobehavioral effects by overcrowding. Adolescent male rats (postnatal day 35±1) were subjected to overcrowding and/or injected with ethanol, 2 g/kg, 20% w/v, (i.p.) for one week. 24 h after the last dose, motor, exploratory behavior, sociability and fear responses were assessed using open field, social interaction and defensive probe burying tests, respectively. Wet brain tissue nitric oxide and reduced glutathione contents as well as monoamine levels, namely dopamine, norepinephrine and serotonin, in addition to 5-HIAA were estimated. Overcrowding increased social play and freezing time. Alcohol administration under overcrowding condition impaired sociability and interfered with active fear response. Alcohol in normal or in under overcrowding condition, impaired motor and exploratory behavior and increased anxiety. These results indicate that concomitant exposure of male adolescent rats to overcrowding and alcohol induced adverse behavioral changes.