Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats
Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats
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DOI：
10.1007/s00213-016-4351-5
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发表时间：
2016-07
影响因子：
3.4
通讯作者：
Zhemeng Wu;Yu Ding;Hongxiao Jia;Liang Li
中科院分区：
文献类型：
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作者：
Zhemeng Wu;Yu Ding;Hongxiao Jia;Liang Li
惊恐前脉冲抑制（PPI）是在惊吓刺激之前，通过较弱的感觉刺激（前脉冲）抑制惊吓反射。在精神分裂症患者中，PPI的注意力调节受损，而不是基线PPI受损，与症状严重程度相关。在大鼠中，前脉冲的恐惧条件化以及条件化前脉冲与噪声掩蔽物之间的知觉空间分离都增强了PPI（PPI的注意调节范例）。目的作为精神分裂症的神经发育模型，隔离饲养损害了大鼠的基础PPI和PPI的注意调节。本研究探讨在Sprague-Dawley雄性大鼠是否atremally blockingN-甲基-d-天冬氨酸（NMDA）受体，特别是影响注意力的PPI调制adultory.ResultsBoth社会饲养的大鼠与新生儿接触的NMDA受体拮抗剂MK-801和隔离饲养的大鼠表现出增强惊吓反应，但只有隔离饲养受损的基线PPI。恐惧条件反射的前脉冲增强PPI在社会饲养的大鼠，但MK-801治疗的大鼠失去了前脉冲功能的特异性。感知空间分离的条件前脉冲和噪声掩蔽进一步增强PPI只在正常饲养的大鼠。氯氮平管理在成年期普遍削弱惊吓，增强基线PPI在martagally中断大鼠，恢复恐惧条件诱导的PPI增强隔离饲养大鼠的前脉冲特征特异性的损失。氯氮平管理也取消了知觉分离诱导的PPI增强正常饲养的大鼠和恐惧条件诱导的PPI增强MK-801-treated rats.Conclusionsisolation饲养损害基线PPI和注意力调节的PPI，但神经系统破坏NMDA受体介导的传输具体损害注意力调节的PPI。氯氮平的缓解作用有限。
RationalPrepulse inhibition (PPI) is suppression of the startle reflex by a weaker sensory stimulus (prepulse) preceding the startling stimulus. In people with schizophrenia, impairment of attentional modulation of PPI, but not impairment of baseline PPI, is correlated with symptom severity. In rats, both fear conditioning of prepulse and perceptually spatial separation between the conditioned prepulse and a noise masker enhance PPI (the paradigms of attentional modulation of PPI).ObjectivesAs a neurodevelopmental model of schizophrenia, isolation rearing impairs both baseline PPI and attentional modulations of PPI in rats. This study examined in Sprague-Dawley male rats whether neonatally blockingN-methyl-d-aspartate (NMDA) receptors specifically affects attentional modulations of PPI during adulthood.ResultsBoth socially reared rats with neonatal exposure to the NMDA receptor antagonist MK-801 and isolation-reared rats exhibited augmented startle responses, but only isolation rearing impaired baseline PPI. Fear conditioning of the prepulse enhanced PPI in socially reared rats, but MK-801-treated rats lost the prepulse feature specificity. Perceptually spatial separation between the conditioned prepulse and a noise masker further enhanced PPI only in normally reared rats. Clozapine administration during adulthood generally weakened startle, enhanced baseline PPI in neonatally interrupted rats, and restored the fear conditioning-induced PPI enhancement in isolation-reared rats with a loss of the prepulse feature specificity. Clozapine administration also abolished both the perceptual separation-induced PPI enhancement in normally reared rats and the fear conditioning-induced PPI enhancement in MK-801-treated rats.ConclusionsIsolation rearing impairs both baseline PPI and attentional modulations of PPI, but neonatally disrupting NMDA receptor-mediated transmissions specifically impair attentional modulations of PPI. Clozapine has limited alleviating effects.