Antidepressant-Like Effect of 1α-Hydroxyvitamin D₃ on Mice in the Forced Swimming Test

Abstract

SummaryWe examined the effect of 1a-hydroxyvitamin D3 [1a(OH)D3] on mice in the forced swimming test. Intragastric administration of 1.0 mg/kg of 1a(OH)D3 reduced immobility time in the forced swimming test. At all concentrations tested (0.5, 1.0, 2.0 mg/kg), 1a(OH)D3 had no effect on locomotor activity, compared with controls. These results suggest that 1a(OH)D3 may have antidepressant-like activity. Key Words 1a-hydroxyvitamin D3, forced swimming test, glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor Depression is a global problem associated with multiple social and health issues (1). Medical treatment of depression is mostly unsatisfactory, as exemplified by a recent re-analysis demonstrating the ineffectiveness of a highly promoted class of drugs used for treating depression (2). A more effective drug not belonging to the antidepressant class is expected in the near future. The relationship between depression and vitamin D has become a topic of research interest in recent years.The likelihood of depression in subjects with vitamin D deficiency is significantly higher than in subjects who are vitamin D sufficient (3). Mean 25-hydroxyvitamin D levels were shown to be markedly lower in patients with minor and major depression than in healthy subjects (4). A clear clinical link between vitamin D and depression has not been established, however. Lansdowne and Provost investigated healthy subjects in the winter, when vitamin D is at low concentrations, and confirmed that mood could be improved when a healthy person is given vitamin D at 400 or 800 IU during winter (5). Furthermore, it was reported that a single dose of 300,000 IU of vitamin D decreases the severity of depression in elderly patients who are taking antidepressants (6). The combination of vitamin D and fluoxetine was shown to be significantly more effective for patients with major depressive disorder than fluoxetine alone (7). To date, however, no reports have been published demonstrating the effect of administration of vitamin D alone on patients with major depressive disorder. Therefore, it is necessary to examine the effect of vitamin D on the depressive state. Almost all antidepressant drugs reduce the immobility time of rats in the forced swimming test (8). Following administration, 1a-hydroxyvitamin D3 [1a(OH)D3] is metabolized in the liver to 1a,25-dihydroxyvitamin D3 [1a,25(OH)2D3], which shows an effect through 1a,25(OH)2D3 receptor (vitamin D3 receptor) distributed over the body (9) including the central nervous system (10). Therefore, we examined the effect of 1a(OH)D3 using the depression model described by Porsolt et al. (8). Materials and MethodsA total of 40 male 5-wk-old ICR mice were obtained from Charlies River Laboratory Co., Ltd. (Kyoto, Japan) 1 wk before the experiment. The mice were housed in plastic cages (3 mice/cage) with sterilized wood chips as bedding in an air-conditioned room maintained at 2362˚C and 5565% humidity with a 12-h alternating light and dark cycle. The mice were fed a commercial...

Vitamins C and D Exhibit Similar Antidepressant Effects to Escitalopram Mediated by NOx and FKBPL in a Stress-Induced Mice Model

“…Similarly, vitamin D has been linked to depression, and low vitamin D levels have been linked to depressive symptoms [ 7 ]. In line with our findings, previous studies showed that acute [ 35 ], and chronic administration of vitamin D in animals [ 36 ] resulted in a reduction in the immobility time in the forced swim test. Moreover, vitamin D deficiency in mice resulted in depressive symptoms [ 37 ].…”

Effects of Magnesium Oxide on the Serum Duloxetine Concentration and Antidepressant-Like Effects of Duloxetine in Rats

“…5,6) In addition, magnesium ions, which are generated when MgO is dissolved, form chelate complexes with dicumarol, such as warfarin, and quinolone antibacterial agents, such as ciprofloxacin. [7][8][9] These physicochemical interactions are considered to interfere with the efficacy of duloxetine by affecting its absorption, but no previous studies have examined the interactions between duloxetine and MgO.…”