Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention
Detection of visual signals by rats: effects of chlordiazepoxide and cholinergic and adrenergic drugs on sustained attention
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DOI：
10.1007/s002130050446
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发表时间：
1997-12-01
影响因子：
3.4
通讯作者：
Padnos, BK
中科院分区：
文献类型：
--
作者：
Bushnell, PJ;Oshiro, WM;Padnos, BK
中枢胆碱能和肾上腺素能通路支持检测和报告暂时不可预测的刺激所必需的注意过程。为了评估药理学操作对这些通路的功能影响，雄性Long-Evans大鼠进行了两种选择：在离散试验信号检测任务中，在出现信号（300毫秒的闪光）后按下一个杠杆提供食物，在没有信号的试验结束时按下第二个杠杆。在每次I-h会话中，在三个100个试验块中以伪随机顺序呈现七个信号强度。在获得稳定的性能基线后，评估氯氮吡酯（0,3,5,8 mg/kg IP），匹罗卡平（0,1.0,1.8,3.0 mg/kg SC），东莨菪碱（0,0.030,0.056,0.100 mg/kg SC），尼古丁（0,0.08,0.25,0.75 mg/kg SC），美甲胺（0,1.8,3.0:5.6 mg/kg SC），可乐定（0,0.003,0.010,0.030 mg/kg SC）和咪唑嗪（0,1,3,10 mg/kg SC）的急性效应。分析了五个绩效指标：响应失败；“命中”的比例[P（命中）：信号试验中正确反应的比例]；“误报”比例[P(fa)：非信号试验中错误反应的比例]；以及命中和正确拒绝的响应时间（RT）。所有减慢反应的药物对命中RT和纠正排斥反应的影响相同，表明运动减慢对选择准确性的影响很小或没有影响。氯二氮环氧化物仅在低信号强度下降低P(hit)，而不影响P（fa）或RT，与感觉损伤（视觉敏感性降低）一致。除尼古丁外，所有其他药物都优先降低高信号强度下的P(hit)，表明损伤的非视觉来源。东莨菪碱、甲胺和可乐定对P（hit）和P（fa）均有影响；匹洛卡品和咪唑嗪降低P(hit)，但不影响P（fa）。在第一批试验中，0.75 mg/kg尼古丁可降低P(hit)；0.08 mg/kg时，使第二区块P（命中）增加；无剂量影响P（fa）。匹罗卡品、东莨菪碱、甲胺和可乐定均可增加RTs，而尼古丁和咪唑嗪则无此作用。这些数据表明，降低胆碱能或肾上腺素能张力的药物（东莨菪碱、美甲胺和可乐定）通过降低信号的检测和增加误报率来损害持续注意，而提高胆碱能或肾上腺素能张力的药物（匹罗卡品、尼古丁和咪唑嗪）通过损害信号的检测来降低注意力，但不影响误报率。相比之下，促进gaba的药物氯二氮环氧化物似乎影响视觉阈值而不是注意力。
Central cholinergic and adrenergic pathways support the attentional processes necessary for detecting and reporting temporally unpredictable stimuli. To assess the functional effects of pharmacological manipulations of these pathways, male Long-Evans rats performed a two-choice: discrete-trial signal-detection task in which food was provided for pressing one lever after presentation of a signal (a 300-ms light flash), and for pressing a second lever at the end of a trial lacking a signal. Seven signal intensities were presented during each I-h session in a pseudo-random order across three 100-trial blocks. After acquisition of a stable performance baseline, the acute effects of chlordiazepoxide (0, 3, 5, 8 mg/kg IP), pilocarpine (0, 1.0, 1.8, 3.0 mg/kg SC), scopolamine (0, 0.030, 0.056, 0.100 mg/kg SC), nicotine (0, 0.08, 0.25, 0.75 mg/kg SC), mecamylamine (0, 1.8, 3.0: 5.6 mg/kg IP), clonidine (0, 0.003, 0.010, 0.030 mg/kg SC), and idazoxan (0, 1, 3, 10 mg/kg SC) were assessed. Five measures of performance were analyzed: response failures; the proportion of "hits" [P(hit): the proportion of correct responses on signal trials]; the proportion of "false-alarms" [P(fa): the proportion of incorrect responses on non-signal trials]; and response times (RT) for hits and for correct rejections. All drugs which slowed responding affected RT for hits and correct rejections equivalently, suggesting little or no influence of motor slowing on choice accuracy. Chlordiazepoxide reduced P(hit) at low signal intensities only, without affecting P(fa) or RT, consistent with sensory impairment (reduced visual sensitivity). All other drugs except nicotine reduced P(hit) at high signal intensities preferentially, suggesting a non-visual source of the impairment. Scopolamine, mecamylamine and clonidine affected both P(hit) and P(fa); pilocarpine and idazoxan reduced P(hit) without affecting: P(fa). Nicotine at 0.75 mg/kg decreased P(hit) in the first block of trials; at 0.08 mg/kg it increased P(hit) in the second block; no dose affected P(fa). RTs were increased by pilocarpine, scopolamine, mecamylamine and clonidine, but not by nicotine or idazoxan. The data suggest that drugs which reduce cholinergic or adrenergic tone (scopolamine, mecamylamine and clonidine) impair sustained attention by decreasing the detection of signals and by increasing the false alarm rate, whereas drugs which elevate cholinergic or adrenergic tone (pilocarpine, nicotine and idazoxan) decrease attention by impairing detection of signals without affecting the false alarm rate. In contrast, the GABA-facilitating drug chlordiazepoxide appeared to affect visual thresholds rather than attention.