Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring

被引:45
作者
James P. Kesby
Jonathan C. O’Loan
Suzanne Alexander
Chao Deng
Xu-Feng Huang
John J. McGrath
Darryl W. Eyles
Thomas H. J. Burne
机构
[1] Queensland Brain Institute, University of Queensland, Brisbane
[2] Queensland Centre for Mental Health Research, Wacol
[3] Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong
[4] Schizophrenia Research Institute, Darlinghurst
[5] Discipline of Psychiatry, University of Queensland, Brisbane
基金
英国医学研究理事会;
关键词
Animal model; Locomotion; MK-801; NMDA receptor; Prepulse inhibition; Schizophrenia; Vitamin D;
D O I
10.1007/s00213-011-2492-0
中图分类号
学科分类号
摘要
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 DVD-deficient rats and an enhanced locomotor response to the N-methyl-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 NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders. © 2011 Springer-Verlag.
引用
收藏
页码:455 / 463
页数:8
相关论文
共 47 条
[1]  
Adams B., Moghaddam B., Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine, Journal of Neuroscience, 18, 14, pp. 5545-5554, (1998)
[2]  
Al-Amin H.A., Weinberger D.R., Lipska B.K., Exaggerated MK-801-induced motor hyperactivity in rats with the neonatal lesion of the ventral hippocampus, Behavioural Pharmacology, 11, 3-4, pp. 269-278, (2000)
[3]  
Al-Amin H.A., Shannon Weickert C., Weinberger D.R., Lipska B.K., Delayed onset of enhanced MK-801-induced motor hyperactivity after neonatal lesions of the rat ventral hippocampus, Biological Psychiatry, 49, 6, pp. 528-539, (2001)
[4]  
Andine P., Widermark N., Axelsson R., Nyberg G., Olofsson U., Martensson E., Sandberg M., Characterization of MK-801-induced behavior as a putative rat model of psychosis, Journal of Pharmacology and Experimental Therapeutics, 290, 3, pp. 1393-1408, (1999)
[5]  
Angrist B., Van Kammen D.P., CNS stimulants as tools in the study of schizophrenia, Trends in Neurosciences, 7, 10, pp. 388-390, (1984)
[6]  
Bakshi V.P., Geyer M.A., Multiple limbic regions mediate the disruption of prepulse inhibition produced in rats by the noncompetitive NMDA antagonist dizocilpine, Journal of Neuroscience, 18, 20, pp. 8394-8401, (1998)
[7]  
Bast T., Zhang W., Feldon J., White I.M., Effects of MK801 and neuroleptics on prepulse inhibition: Re-examination in two strains of rats, Pharmacology Biochemistry and Behavior, 67, 3, pp. 647-658, (2000)
[8]  
Burne T.H.J., Becker A., Brown J., Eyles D.W., Mackay-Sim A., McGrath J.J., Transient prenatal Vitamin D deficiency is associated with hyperlocomotion in adult rats, Behavioural Brain Research, 154, 2, pp. 549-555, (2004)
[9]  
Burne T.H.J., Feron F., Brown J., Eyles D.W., McGrath J.J., Mackay-Sim A., Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle, Physiology and Behavior, 81, 4, pp. 651-655, (2004)
[10]  
Burne T.H.J., O'Loan J., McGrath J.J., Eyles D.W., Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint, Behavioural Brain Research, 174, 1, pp. 119-124, (2006)