Giménez-Llort Lydia, Cañete Toni, Guitart-Masip Marc, Fernández-Teruel Alberto, Tobeña Adolf
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neuroscience, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Physiol Behav. 2005 Nov 15;86(4):458-66. doi: 10.1016/j.physbeh.2005.07.021. Epub 2005 Sep 9.
Strain differences in spontaneous locomotor activity and the behavioral patterns induced by dopaminergic agonists in rodents can disclose differential genetic susceptibilities to dopaminergic dysfunction (i.e. vulnerability to psychosis). Psychogenetic selection of hypoemotional Roman High-Avoidance (RHA) and hyperemotional Low-Avoidance (RLA) rats leads to divergence in dopaminergic function as well. The present study was designed to characterize their spontaneous activity and their responses to apomorphine (0.067-3 mg/kg, s.c.) as compared to those of the standard Sprague-Dawley (SD) strain. The Roman strains displayed higher spontaneous activity than SD rats and RHA exhibited the higher response to novelty which agrees with a higher sensitivity to apomorphine in this strain. The biphasic effect induced by apomorphine (locomotor inhibition and yawning at low doses but stimulation of locomotion and stereotyped behavior at higher ones) was reproduced in the standard SD strain. Low doses were less effective inducing locomotor inhibition in RHA whereas these animals were much more sensitive to high dose-induced stereotyped behavior. In contrast, RLA was characterized as a high-yawning strain and low doses of apomorphine also induced a striking motor inhibition suggesting functional enhancement of dopamine receptors mediating these behaviors. The detailed and distinctive behavioral profiles described in this work suggest between strain differences both at the presynaptic and postsynaptic dopaminergic function and may serve as paths to better specify functional mechanisms in future studies of risk of developing dopaminergic dysfunctions.
啮齿动物自发运动活动的品系差异以及多巴胺能激动剂诱导的行为模式差异,能够揭示对多巴胺能功能障碍的不同遗传易感性(即对精神病的易感性)。对低情感的罗马高回避(RHA)大鼠和高情感的低回避(RLA)大鼠进行心理遗传学选择,也会导致多巴胺能功能的差异。本研究旨在表征它们的自发活动以及与标准斯普拉格-道利(SD)品系相比,它们对阿扑吗啡(0.067 - 3毫克/千克,皮下注射)的反应。罗马品系的自发活动高于SD大鼠,且RHA对新奇事物表现出更高的反应,这与该品系对阿扑吗啡的更高敏感性一致。阿扑吗啡诱导的双相效应(低剂量时运动抑制和打哈欠,但高剂量时刺激运动和刻板行为)在标准SD品系中也能重现。低剂量在RHA中诱导运动抑制的效果较差,而这些动物对高剂量诱导的刻板行为更为敏感。相比之下,RLA被表征为一个高打哈欠品系,低剂量的阿扑吗啡也会诱导明显的运动抑制,表明介导这些行为的多巴胺受体功能增强。这项工作中描述的详细且独特的行为特征表明,在突触前和突触后多巴胺能功能方面存在品系差异,并且可能为未来多巴胺能功能障碍风险研究中更好地确定功能机制提供途径。