Prenatal vitamin D Deficiency causes behavioural changes in adult offspring: Evidence of dopaminergic dysregulation

Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.