Galizio Mark, Mathews Michael, Mason Madeleine, Panoz-Brown Danielle, Prichard Ashley, Soto Paul
University of North Carolina Wilmington, United States.
University of North Carolina Wilmington, United States.
Neurobiol Learn Mem. 2017 Nov;145:67-74. doi: 10.1016/j.nlm.2017.09.006. Epub 2017 Sep 8.
The odor span task is an incrementing non-matching-to-sample procedure designed to provide an analysis of working memory capacity in rodents. The procedure takes place in an arena apparatus and rats are exposed to a series of odor stimuli in the form of scented lids with the selection of new stimuli reinforced. This procedure makes it possible to study drug effects as a function of the number of stimuli to remember. In the present study, the non-selective positive allosteric GABA receptor modulator flunitrazepam impaired odor span performance at doses that did not affect a control odor discrimination. In contrast, the alpha-1 selective positive GABA receptor modulator zolpidem and the cholinergic receptor antagonist scopolamine only impaired odor span at doses that produced more global impairment, including decreased accuracy in the control discrimination and increased response omissions in the both the odor span and control discrimination procedures. Even though the effects of flunitrazepam were selective to odor span performance, they did not depend on the number of stimuli to remember-the same degree of impairment occurred regardless of the memory load. These findings suggest that flunitrazepam interfered selectively with conditional discrimination performance rather than working memory and tentatively suggest that flunitrazepam's selective effects in the odor span task relative to the control odor discrimination are mediated by one or more non-alpha1 GABA receptor subtypes.
气味跨度任务是一种递增式样本非匹配程序,旨在分析啮齿动物的工作记忆能力。该程序在一个竞技场装置中进行,大鼠会接触一系列带有香味盖子形式的气味刺激,并对选择新刺激的行为给予强化。此程序使得研究药物效应与需记忆刺激数量之间的关系成为可能。在本研究中,非选择性正性变构GABA受体调节剂氟硝西泮在不影响对照气味辨别能力的剂量下损害了气味跨度表现。相比之下,α-1选择性正性GABA受体调节剂唑吡坦和胆碱能受体拮抗剂东莨菪碱仅在产生更广泛损害的剂量下才损害气味跨度,包括对照辨别准确性降低以及在气味跨度和对照辨别程序中反应遗漏增加。尽管氟硝西泮的效应对气味跨度表现具有选择性,但它们并不取决于需记忆的刺激数量——无论记忆负荷如何,都会出现相同程度的损害。这些发现表明,氟硝西泮选择性地干扰了条件辨别表现而非工作记忆,并初步表明氟硝西泮在气味跨度任务中相对于对照气味辨别所产生的选择性效应是由一种或多种非α1 GABA受体亚型介导的。