Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring
Rationale Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVDdeficient rats and an enhanced locomotor response to the Nmethyl- D-aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK- 801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. Methods DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. Results DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. Conclusions These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDAmediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.