Developmentally vitamin D-deficient rats show enhanced prepulse inhibition after acute Δ9-tetrahydrocannabinol
Developmentally vitamin D-deficient rats show enhanced prepulse inhibition after acute Δ9-tetrahydrocannabinol
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DOI：
10.1097/fbp.0000000000000041
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发表时间：
2014-06-01
影响因子：
1.6
通讯作者：
McGrath, John J.
中科院分区：
文献类型：
--
作者：
Burne, Thomas H. J.;Alexander, Suzanne;McGrath, John J.
发展性维生素D （DVD）缺乏被认为是精神分裂症的一个危险因素。dvd缺陷大鼠在急性使用安非他明和MK-801等拟精神药物治疗后表现出选择性认知缺陷和新事物诱导的过度运动和增强的运动反应。在这里，我们的目的是研究一种来自不同类别的拟精神/精神活性化合物的药物，德尔塔(9)-四氢大麻酚（THC），在与精神分裂症的认知和阳性症状相关的任务中的作用。本研究的目的是探讨DVD缺乏是否调节四氢大麻酚对延迟依赖记忆、感觉运动门控和运动测试的行为影响。成年对照和dvd缺陷大鼠在进行可变延迟（0-24 s）的DMTS任务前15分钟注射四氢大麻酚（0、0.3、0.6、1.25、2.5 mg/kg）。另一组大鼠分别注射2.5 mg/kg四氢大麻酚或载药，然后进行声惊反应的脉冲前抑制（PPI）测试或在空旷场地进行。对照大鼠和dvd缺陷大鼠在DMTS上表现出类似的剂量依赖性损伤。在所有延迟（0-24 s）中，2.5 mg/kg剂量的损伤最大。dvd缺失大鼠表现出四氢大麻酚诱导的PPI增强，而对照组大鼠未见此现象。母性饮食对大鼠野外的声惊吓反应和运动反应没有影响。本研究报告了新的发现，即dvd缺乏大鼠对四氢大麻酚对PPI的急性影响更敏感。似乎产前维生素D缺乏对大麻素行为影响的敏感性有长期影响。
Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, Delta(9)-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids.