PREPULSE INHIBITION OF THE ACOUSTIC STARTLE RESPONSE OF RATS IS REDUCED BY 6-HYDROXYDOPAMINE LESIONS OF THE MEDIAL PREFRONTAL CORTEX
PREPULSE INHIBITION OF THE ACOUSTIC STARTLE RESPONSE OF RATS IS REDUCED BY 6-HYDROXYDOPAMINE LESIONS OF THE MEDIAL PREFRONTAL CORTEX
复制标题
DOI：
10.1007/bf02245228
复制
发表时间：
1994-01-01
影响因子：
3.4
通讯作者：
KOCH, M
中科院分区：
文献类型：
--
作者：
BUBSER, M;KOCH, M
前脉冲抑制（PPI）的声惊吓反应（ASR）的损害多巴胺（DA）的过度活跃的中脑核和前内侧纹状体。由于有证据表明内侧前额叶皮质中的DA对纹状体DA系统施加抑制性控制，因此研究了前额叶DA的耗尽是否会降低PPI。在前额叶皮质注射（每侧2 × 1 μ l）赋形剂、低剂量（3.0 μ g/μ l）或高剂量（6.0 μ g/μ l）6-羟基多巴胺氢溴酸盐（6-OHDA）之前和之后，对大鼠进行PPI测试。只有高剂量的6-OHDA，导致87%的前额叶DA消耗，损害PPI。声预脉冲（75 dB，10 kHz）减少对惊吓脉冲（100 dB噪声突发）的反应的能力在假损伤大鼠中得以维持，但在高剂量6-OHDA损伤的大鼠中受到显著干扰。6-OHDA处理在没有前脉冲的情况下不影响ASR幅度。PPI的减少与DA耗竭的程度相关。这些结果表明，DA神经支配的前额叶皮层参与调制的ASR，他们提供了进一步的证据，相反的行动，前额叶和皮层下DA系统的行为控制。目前的研究结果进行了讨论方面的潜在作用，前额叶DA在精神分裂症。
Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 x 1 mu l per side) of vehicle, a low (3.0 mu g/mu l) or a high (6.0 mu g/mu l) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.