Rutter John J, Devilbiss David M, Waterhouse Barry D
Truman State University, 100 E. Normal Street, Kirksville, MO 63501, USA.
Eur J Neurosci. 2005 Dec;22(12):3205-16. doi: 10.1111/j.1460-9568.2005.04500.x.
Previous studies have shown that systemic administration of cocaine transiently alters stimulus-evoked responses of ventral posteromedial (VPM) thalamic neurons. Results from these single-unit electrophysiological studies revealed that cocaine was equally likely to augment or attenuate the magnitude of sensory evoked responses following threshold level stimulation of peripheral receptive fields. In an attempt to clarify the impact of cocaine administration on sensory signal processing, we examined the drug's effects on responses of individual neurons and ensembles of VPM thalamic neurons to sensory stimuli, and performance of subjects in a sensory detection behavioural task. Extracellular responses of single (n = 1 cell/rat) or multiple VPM thalamic neurons (n = 10-40 cells/rat) were monitored before and after cumulative doses of cocaine (0.25-2.0 mg/kg i.v.). Neuronal responses were characterized by assessing the response profile to a range of peri-threshold-level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, determined from quantitative analysis of spike train data, indicated that whereas cocaine elicits variable effects at the single cell level, the stimulus-evoked response of the recorded population was likely to increase following lower (0.25-1.0 mg/kg i.v.) doses of cocaine. Furthermore, cocaine preferentially enhanced responses to smaller magnitude deflections of vibrissa, altering the response profile from a mode that accurately conveyed stimulus strength to one that increased detection at the expense of discrimination. Finally, a similar pattern emerged in a behavioural paradigm involving rats trained to detect variable amplitude whisker pad stimulation, suggesting a common action of cocaine that may contribute to the drug's addictive properties.
先前的研究表明,全身性给予可卡因会短暂改变腹后内侧(VPM)丘脑神经元的刺激诱发反应。这些单单位电生理研究的结果显示,在对周围感受野进行阈值水平刺激后,可卡因增强或减弱感觉诱发反应幅度的可能性相同。为了阐明可卡因给药对感觉信号处理的影响,我们研究了该药物对VPM丘脑单个神经元和神经元群体对感觉刺激的反应的影响,以及对受试者在感觉检测行为任务中的表现的影响。在累积给予可卡因(0.25 - 2.0 mg/kg静脉注射)之前和之后,监测单个(n = 1个细胞/只大鼠)或多个VPM丘脑神经元(n = 10 - 40个细胞/只大鼠)的细胞外反应。通过评估对同侧面部最佳触须一系列阈周水平偏转的反应特征来表征神经元反应。从尖峰序列数据的定量分析确定的药物对刺激 - 反应曲线的影响表明,虽然可卡因在单细胞水平上引起可变效应,但在给予较低剂量(0.25 - 1.0 mg/kg静脉注射)的可卡因后,记录群体的刺激诱发反应可能会增加。此外,可卡因优先增强对触须较小幅度偏转的反应,将反应特征从准确传达刺激强度的模式改变为以牺牲辨别力为代价增加检测的模式。最后,在涉及训练大鼠检测可变幅度触须垫刺激的行为范式中出现了类似的模式,这表明可卡因的一种共同作用可能导致该药物的成瘾特性。