Muir J L, Robbins T W, Everitt B J
Department of Experimental Psychology, University of Cambridge, UK.
Psychopharmacology (Berl). 1992;107(4):541-50. doi: 10.1007/BF02245269.
The behavioral effects of GABAergic manipulation of the basal forebrain were investigated using two behavioral tasks, which previous studies have shown to yield dissociable effects following quisqualate-induced lesions of the basal forebrain: a five-choice serial reaction time task, involving approaching the location of a brief visual stimulus that is associated with reward; and a conditional visual discrimination task, requiring retrieval of information about a discriminative stimulus that stays constant over time. Following acquisition of the tasks, chronic guide cannulae were stereotaxically implanted into the basal forebrain. Those animals trained on the conditional visual discrimination task showed a dose-dependent reduction in choice accuracy and a lengthening of latency to respond correctly to the visual stimulus following administration of the GABA-A agonist, muscimol (1, 2, 3 ng/microliters/hem). While certain of these deficits, for example response latency, could be restored to control levels by co-administration of the GABA-A antagonist, bicuculline, none of the behavioural impairments could be significantly attenuated by systemic by systemic co-administration of the cholinesterase inhibitor, physostigmine (0.05, 0.1, 0.2 mg/kg, IP). Similarly, a dose dependent effect of muscimol (1, 1.5, 2 ng/microliters/hem) on choice accuracy and correct response latency was observed on performance of the five-choice attentional task. However, in contrast to the conditional task, significant attenuation of the impairment in choice accuracy was obtained following administration of physostigmine (0.05 and 0.1 mg/kg). Attenuation of muscimol-induced deficits by administration of bicuculline was also observed. It is therefore evident that although manipulation of GABAergic activity in the region of the basal forebrain produces profound deficits in different tasks of cognitive function, only some of these may be due to modulation of the magnocellular cholinergic projection to the neocortex.
利用两项行为任务研究了基底前脑GABA能操纵的行为效应，先前的研究表明，在基底前脑的喹啉酸诱导损伤后，这两项任务会产生可分离的效应：一项是五选择连续反应时任务，涉及接近与奖励相关的短暂视觉刺激的位置；另一项是条件视觉辨别任务，需要检索关于随时间保持不变的辨别刺激的信息。在完成这些任务后，将慢性引导套管立体定位植入基底前脑。那些接受条件视觉辨别任务训练的动物在给予GABA-A激动剂蝇蕈醇（1、2、3纳克/微升/半球）后，选择准确性出现剂量依赖性降低，对视觉刺激正确反应的潜伏期延长。虽然其中一些缺陷，例如反应潜伏期，可以通过同时给予GABA-A拮抗剂荷包牡丹碱恢复到对照水平，但通过全身同时给予胆碱酯酶抑制剂毒扁豆碱（0.05、0.1、0.2毫克/千克，腹腔注射），没有一种行为损伤能得到显著减轻。同样，在五选择注意力任务的表现中观察到蝇蕈醇（1、1.5、2纳克/微升/半球）对选择准确性和正确反应潜伏期的剂量依赖性效应。然而，与条件任务不同的是，给予毒扁豆碱（0.05和0.1毫克/千克）后，选择准确性的损伤得到了显著减轻。也观察到给予荷包牡丹碱可减轻蝇蕈醇诱导的缺陷。因此，很明显，尽管操纵基底前脑区域的GABA能活性会在不同的认知功能任务中产生严重缺陷，但其中只有一些可能是由于对新皮层的大细胞胆碱能投射的调节所致。
