Smythe J W, Murphy D, Bhatnagar S, Timothy C, Costall B
Department of Pharmacology, University of Bradford, UK.
Pharmacol Biochem Behav. 1996 May;54(1):57-63. doi: 10.1016/0091-3057(95)02130-2.
Central cholinergic (ACh) projections have been shown to modulate stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis and are integral to the expression of electrophysiological correlates of arousal, namely hippocampal theta rhythm. The degree to which these actions of ACh are behaviorally relevant has received comparatively less attention, and we sought to investigate if manipulations of ACh systems might also affect behaviors related to stress and arousal. We chose to examine indices of anxiety as revealed by changes in behavior elicited by the black-white box test, a relatively novel and recently validated model of rodent anxiety. Groups of rats were injected with either scopolamine hydrobromide (SCOP; 0, 0.05, and 0.10 mg/kg i.p.) or the peripherally acting scopolamine methyl bromide (methyl-SCOP; 0, 0.05, and 0.10 mg/kg i.p.) to compare and contrast the effects of central and peripheral ACh blockade on measures of anxiety. SCOP pretreatment significantly lowered latencies for rats to escape from the white to black compartment, while methyl-SCOP elevated latencies to reenter the white chamber from the black. Both drugs increased the amount of time rats spent in the black compartment and also suppressed exploration as revealed by decreased episodes of intercompartmental locomotion. Neither drug deleteriously affected locomotor activity, however; in fact, SCOP significantly increased locomotion in the white chamber. In the absence of motor disturbances to account for any group differences, we contend that both central and peripheral ACh blockade may affect measures of anxiety, perhaps by directly or indirectly affecting HPA activity. Central ACh systems may underlie sensory filtering whereby irrelevant stimuli are excluded from sensory processing. Antagonism of ACh transmission may render an animal incapable of correctly processing sensory information leading to hyperresponsiveness, which can manifest itself as enhanced anxiety and fear.
中枢胆碱能（乙酰胆碱，ACh）投射已被证明可调节应激诱导的下丘脑 - 垂体 - 肾上腺（HPA）轴的激活，并且对于觉醒的电生理相关指标（即海马θ节律）的表达不可或缺。ACh的这些作用在行为上的相关程度相对较少受到关注，我们试图研究对ACh系统的操作是否也可能影响与应激和觉醒相关的行为。我们选择通过黑白箱试验所引发的行为变化来检查焦虑指标，黑白箱试验是一种相对新颖且最近经过验证的啮齿动物焦虑模型。给大鼠组腹腔注射氢溴酸东莨菪碱（SCOP；0、0.05和0.10mg/kg）或外周作用的甲基溴化东莨菪碱（甲基 - SCOP；0、0.05和0.10mg/kg），以比较和对比中枢和外周ACh阻断对焦虑测量指标的影响。SCOP预处理显著降低了大鼠从白色隔室逃到黑色隔室的潜伏期，而甲基 - SCOP则延长了从黑色隔室重新进入白色隔室的潜伏期。两种药物都增加了大鼠在黑色隔室中停留的时间，并且还通过减少隔室间移动发作次数抑制了探索行为。然而，两种药物均未对运动活动产生有害影响；事实上，SCOP显著增加了白色隔室中的运动。在不存在运动障碍来解释任何组间差异的情况下，我们认为中枢和外周ACh阻断都可能影响焦虑测量指标，可能是通过直接或间接影响HPA活性。中枢ACh系统可能是感觉过滤的基础，借此无关刺激被排除在感觉处理之外。ACh传递的拮抗作用可能使动物无法正确处理感觉信息，从而导致反应过度，这可能表现为焦虑和恐惧增强。
