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黑质网状部γ-氨基丁酸参与操作性杠杆按压的调节:药理学与微透析研究

Substantia nigra pars reticulata GABA is involved in the regulation of operant lever pressing: pharmacological and microdialysis studies.

作者信息

Correa M, Mingote S, Betz A, Wisniecki A, Salamone J D

机构信息

Department of Psychology, University of Connecticut, 06269-1020, Storrs, CT, USA.

出版信息

Neuroscience. 2003;119(3):759-66. doi: 10.1016/s0306-4522(03)00117-9.

DOI:10.1016/s0306-4522(03)00117-9
PMID:12809696
Abstract

Substantia nigra pars reticulata (SNr) is an important mesencephalic nucleus that functions as a relay area for basal ganglia output. SNr receives GABAergic inputs from the neostriatum and globus pallidus, and in turn sends projections to a variety of motor areas. Although a large number of studies have focused upon the behavioral functions of basal ganglia dopamine, much less is known about the behavioral functions of SNr GABA. The present studies were undertaken to investigate the role of SNr GABA in lever pressing behavior. In the first experiment, the GABA(A) antagonist bicuculline was infused locally into SNr to determine if blockade of GABA receptors interfered with the performance of lever pressing on a fixed ratio 5 schedule. SNr injections of bicuculline produced a dose-related suppression of operant responding. Analysis of interresponse time bins showed that SNr bicuculline produced a response slowing characterized by a relative reduction in the number of fast interresponse times, and an increase in the relative number of pauses. In an additional experiment, microdialysis methods were used to determine if extracellular GABA is elevated during the performance of fixed ratio five lever pressing. During the 30 min lever pressing session, extracellular GABA showed a significant and substantial increase relative to baseline levels. These data support the hypothesis that SNr GABA is involved in the regulation of motor output, and indicate that GABA release in this structure is increased during behavioral stimulation.

摘要

黑质网状部(SNr)是中脑的一个重要核团,作为基底神经节输出的中继区域发挥作用。SNr接收来自新纹状体和苍白球的GABA能输入,并转而向各种运动区域发出投射。尽管大量研究聚焦于基底神经节多巴胺的行为功能,但对于SNr GABA的行为功能却知之甚少。本研究旨在探讨SNr GABA在杠杆按压行为中的作用。在第一个实验中,将GABA(A)拮抗剂荷包牡丹碱局部注入SNr,以确定GABA受体的阻断是否会干扰固定比例5的杠杆按压表现。向SNr注射荷包牡丹碱会产生与剂量相关的操作性反应抑制。对反应间隔时间区间的分析表明,向SNr注射荷包牡丹碱会导致反应减慢,其特征是快速反应间隔时间的数量相对减少,停顿的相对数量增加。在另一个实验中,使用微透析方法来确定在固定比例5的杠杆按压过程中细胞外GABA是否升高。在30分钟的杠杆按压过程中, 细胞外GABA相对于基线水平呈现出显著且大幅的增加。这些数据支持了SNr GABA参与运动输出调节的假说,并表明在行为刺激期间该结构中的GABA释放增加。

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