Vitamin B12 replacement therapy reduces induced depressive behavior in young rats

Adriana Maria de Oliveira Brito, Amanda Sarah Ferreira de Lima Costa, Sharon Lima Oliveira, Alisson Diego Machado, Eder de Carvalho Pincinato, Carlos Eduardo Moscato Fuzaro, Isabela Rosier Olimpio Pereira


Aims: To assess whether mild vitamin B12 deficiency induces depression prior to the development of anemia, and whether vitamin B12 supplementation can act as a preventive measure against depression in young rats.

Methods: Wistar rats were divided into control group (n=11) and B12 group (n=10). The B12 group received vitamin B12 supplementation in drinking water throughout the study. In Phase 1, all animals received a pectin-supplemented diet (50g/kg) for six weeks to induce vitamin B12 depletion. After that, the Porsolt test was applied for induction and evaluation of depressive state and blood was collected for a complete blood count. In Phase 2, which lasted two weeks, pectin was removed from the diet and the same tests were applied again at the end.

Results: In both phases, erythrocyte count, hematocrit level, and hemoglobin concentration were normal, i.e., the rats did not develop anemia. The forced swim test results at the end of Phase 1 show that the B12 group exhibited shorter immobility time than the control group (0.44±0.32 vs. 0.75±0.18 minutes, p=0.024) and longer swimming time (4.64±0.27 vs. 4.32±0.28 minutes, p=0.013), indicating reduction of depressive state with vitamin B12 replacement therapy. When the groups were compared at the end of Phase 2,  there was no significant difference in any of the forced swim test components.

Conclusions: Mild vitamin B12 deficiency, at a level that did not induce anemia, led to depressive state in young rats where vitamin B12 supplementation reversed the effects of vitamin depletion. Under normal nutritional circumstances, however, vitamin B12 supplementation did not have any effect on depressive state. These findings encourage further studies to investigate the associations between vitamin B12 and depression in young individuals. Moreover, this study also presents perspectives for a new experimental model of depression induced by vitamin B12 depletion.


depression; vitamin B12; rats; disease models, animal; dietary supplementary feeding.


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