Kesby James P, Burne Thomas H J, McGrath John J, Eyles Darryl W
School of Biomedical Science, University of Queensland, Brisbane, Australia.
Biol Psychiatry. 2006 Sep 15;60(6):591-6. doi: 10.1016/j.biopsych.2006.02.033. Epub 2006 May 12.
Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. The behavioral phenotype of adult rats subjected to transient low prenatal vitamin D is characterized by spontaneous hyperlocomotion but normal prepulse inhibition of acoustic startle (PPI). The aim of this study was to examine the impact of selected psychotropic agents and one well-known antipsychotic agent on the behavioral phenotype of DVD deplete rats.
Control versus DVD deplete adult rats were assessed on holeboard, open field and PPI. In the open field, animals were given MK-801 and/or haloperidol. For PPI, the animals were given apomorphine or MK-801.
DVD deplete rats had increased baseline locomotion on the holeboard task and increased locomotion in response to MK-801 compared to control rats. At low doses, haloperidol antagonized the MK-801 hyperactivity of DVD deplete rats preferentially and, at a high dose, resulted in a more pronounced reduction in spontaneous locomotion in DVD deplete rats. DVD depletion did not affect either baseline or drug-mediated PPI response.
These results suggest that DVD deficiency is associated with a persistent alteration in neuronal systems associated with motor function but not those associated with sensory motor gating. In light of the putative association between low prenatal vitamin D and schizophrenia, the discrete behavioral differences associated with the DVD model may help elucidate the neurobiological correlates of schizophrenia.
发育性维生素D(DVD)缺乏已被认为是精神分裂症的一个风险因素。产前短暂维生素D水平低的成年大鼠的行为表型特点是自发活动亢进,但听觉惊跳前脉冲抑制(PPI)正常。本研究的目的是检查选定的精神药物和一种知名抗精神病药物对DVD缺乏大鼠行为表型的影响。
对对照组和DVD缺乏成年大鼠进行洞板试验、旷场试验和PPI评估。在旷场试验中,给动物注射MK-801和/或氟哌啶醇。对于PPI试验,给动物注射阿扑吗啡或MK-801。
与对照大鼠相比,DVD缺乏大鼠在洞板试验中的基线活动增加,对MK-801的反应性活动也增加。低剂量时,氟哌啶醇优先拮抗DVD缺乏大鼠的MK-801诱导的多动,高剂量时,导致DVD缺乏大鼠的自发活动更明显减少。DVD缺乏不影响基线或药物介导的PPI反应。
这些结果表明,DVD缺乏与运动功能相关的神经元系统的持续改变有关,但与感觉运动门控相关的神经元系统无关。鉴于产前维生素D水平低与精神分裂症之间的假定关联,与DVD模型相关的离散行为差异可能有助于阐明精神分裂症的神经生物学相关性。