Bushnell P J
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Neurotoxicol Teratol. 1988 May-Jun;10(3):237-44. doi: 10.1016/0892-0362(88)90023-2.
Working memory was modeled in rats using a delayed response task with spatial location as the discriminative cue. Rats received food for pressing 1 of 2 retractable levers in the choice phase of a trial if that lever had been presented in the prior sample phase of that trial. When delays of 0-20 sec were imposed between sample and choice, choice accuracy declined with increasing delay. With short intertrial intervals (ITIs), choice accuracy decreased more at long delays than at short delays, showing that interference from previous trials impaired memory but not discrimination. Rats emitted overt mediating responses during delay by pressing the levers in the retracted position. However, the frequency of delay presses was low (less than 2/trial in all rats) and neither their frequency nor accuracy was related to choice accuracy. Resetting the delay interval for each delay press did not significantly alter choice response accuracy. Trimethyltin (TMT), 7 mg/kg IV, reduced the choice accuracy of one rat to chance levels at all delays; two other rats were affected transiently. TMT reduced choice accuracy during weeks 1 and 4 postinjection, with significant effects on the linear slope and intercept of the mean retention gradient during week 4. TMT did not affect responses to the retracted levers during delays. TMT treatment also elevated levels of glial fibrillary acidic protein (GFAP) in the CNS, measured 4 weeks after treatment. Hippocampal GFAP correlated highly with the reduction in choice accuracy during week 1 (r = -.903) and week 4 (r = -.797) postTMT.(ABSTRACT TRUNCATED AT 250 WORDS)
利用以空间位置作为辨别线索的延迟反应任务，在大鼠中对工作记忆进行建模。在试验的选择阶段，如果大鼠按压两个可伸缩杠杆中的一个能获得食物，前提是该杠杆在该试验之前的样本阶段出现过。当在样本和选择之间施加0至20秒的延迟时，选择准确性随延迟增加而下降。在短的试验间隔（ITIs）情况下，长延迟时选择准确性的下降幅度大于短延迟时，这表明先前试验的干扰损害了记忆而非辨别能力。大鼠在延迟期间通过按压缩回位置的杠杆发出明显的中介反应。然而，延迟按压的频率很低（所有大鼠均低于每次试验2次），其频率和准确性均与选择准确性无关。为每次延迟按压重置延迟间隔并未显著改变选择反应准确性。静脉注射7mg/kg的三甲基锡（TMT）使一只大鼠在所有延迟情况下的选择准确性降至随机水平；另外两只大鼠受到短暂影响。TMT在注射后第1周和第4周降低了选择准确性，对第4周平均保持梯度的线性斜率和截距有显著影响。TMT在延迟期间不影响对缩回杠杆的反应。TMT处理还使治疗后4周测量的中枢神经系统中胶质纤维酸性蛋白（GFAP）水平升高。海马GFAP与TMT后第1周（r = -0.903）和第4周（r = -0.797）选择准确性的降低高度相关。（摘要截短于250字）
