MODULATION OF THE GATING OF AUDITORY EVOKED-POTENTIALS BY NOREPINEPHRINE - PHARMACOLOGICAL EVIDENCE OBTAINED USING A SELECTIVE NEUROTOXIN
MODULATION OF THE GATING OF AUDITORY EVOKED-POTENTIALS BY NOREPINEPHRINE - PHARMACOLOGICAL EVIDENCE OBTAINED USING A SELECTIVE NEUROTOXIN
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DOI：
10.1016/0006-3223(88)90273-9
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发表时间：
1988-06-01
影响因子：
10.6
通讯作者：
ROSE, GM
中科院分区：
文献类型：
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作者：
ADLER, LE;PANG, K;ROSE, GM
在Sprague-Dawley大鼠中使用诱发电位技术评估感觉门控的中枢机制，该技术类似于我们先前用于显示精神病患者感觉门控减弱的技术。门控机制进行了检查，使用条件测试范式，其中对74分贝点击提供条件和测试刺激之间的间隔为0.5秒。中潜伏期听觉诱发反应（N50）记录从头骨的未麻醉，自由活动的大鼠表现出显着抑制测试点击。安非他明（1 mg/kg，ip）的全身给药显着减少了对测试刺激的反应抑制量;氟哌啶醇（1 mg/kg），安非他明后注射，返回的条件反射测试抑制比向正常值。安非他明还降低了条件反射的潜伏期和振幅，氟哌啶醇也逆转了这种效应。在精神分裂症中观察到测试反应的抑制降低以及条件反射的振幅和潜伏期降低。为了帮助确定这些作用的潜在机制，以1周间隔给予动物两次N-（2-氯乙基-N-乙基-2-溴苄胺）（DSP 4; 50 mg/kg，ip），这是一种选择性消耗中枢去甲肾上腺素的药物。化学分析证实了消耗的程度和选择性。在DSP 4之后，安非他明对条件反射的振幅和潜伏期的影响在很大程度上没有变化。然而，预处理与DSP 4显着衰减条件反射测试抑制观察到的安非他明管理后的减少。这些数据表明去甲肾上腺素在感觉处理的调制中的特定作用。
Central mechanisms of sensory gating were assessed in Sprague-Dawley rats using an evoked potential technique similar to one that we have previously employed to show diminished sensory gating in psychotic patients. Gating mechanisms were examined using a conditioning-testing paradigm in which pairs of 74-dB clicks were delivered; the interval between the conditioning and test stimuli was 0.5 sec. A middle latency auditory evoked response (N50) recorded from the skull of unanesthetized, freely moving rats demonstrated significant suppression to the test click. Systemic administration of amphetamine (1 mg/kg, ip) significantly reduced the amount of suppression of the response to the test stimulus; haloperidol (1 mg/kg), injected after the amphetamine, returned the conditioning-testing suppression ratio toward normal values. Amphetamine also decreased the latency and amplitude of the conditioning response, an effect that was also reversed by haloperidol. Both decreased suppression of the test response and reduced amplitude and latency of the conditioning response have been observed in schizophrenia. To aid in determining the underlying mechanism of these effects, the animals were treated with two doses, given at a 1-week interval, of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine) (DSP4; 50 mg/kg, ip), an agent that selectively depletes central norepinephrine. The extent and selectivity of the depletions were confirmed by chemical analysis. Following DSP4, the effects of amphetamine on the amplitude and latency of the conditioning response were largely unchanged. However, pretreatment with DSP4 significantly attenuated the reduction in conditioning-testing suppression observed following the administration of amphetamine. The data suggest a specific role for norepinephrine in the modulation of sensory processing.