Behavioral Pharmacology Group, Laboratory of Morphology and Pathology Animal Health, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes 28013-600, RJ, Brazil.
Research and Development (151), VA Medical Center and SUNY Upstate Medical University, 800 Irving Avenue, Syracuse, NY 13210, USA.
Pharmacol Biochem Behav. 2017 Aug;159:76-83. doi: 10.1016/j.pbb.2017.07.011. Epub 2017 Jul 21.
The activation of extracellular signal-regulated kinase protein (ERK) has been linked to the adaptive responses to environmental changes and memory. The aim of this study was to measure ERK activation in primary dopamine projection areas namely, the prefrontal cortex and the nucleus accumbens, following a conditioned dopaminergic drug response. Initially, the effect of unconditioned apomorphine (2.0mg/kg) administration on ERK activation was measured and the results showed an increase in ERK for both brain regions. Subsequently, two experiments were conducted to assess ERK activation in these two areas following apomorphine conditioned contextual stimuli. In experiment 1, rats received 5 daily injections of 2.0mg/kg apomorphine or vehicle immediately prior to placement in an open-field. After a withdrawal period of two days, a conditioning test was conducted, in which rats received a 30min non-drug test. Immediately after completion of the test, an immunohistochemical protocol was carried out to measure ERK activation. In experiment 2, a similar test protocol was performed except that the treatments were administered 30min following open-field tests (post-trial experiment). The results showed that the repeated apomorphine treatments given prior to testing induced conditioned effects. An increase in ERK activation was seen in the prefrontal cortex but not in the nucleus accumbens. There was no conditioning response observed in the post-trial experiment and no differential ERK activation. These observations implicate the prefrontal cortex in the associative neuro-adaptive changes induced by dopaminergic stimulation.
细胞外信号调节激酶蛋白(ERK)的激活与环境变化和记忆的适应性反应有关。本研究的目的是测量原发性多巴胺投射区(即前额叶皮层和伏隔核)中 ERK 激活,以适应多巴胺能药物反应。最初,测量了未条件阿扑吗啡(2.0mg/kg)给药对 ERK 激活的影响,结果显示两个脑区的 ERK 均增加。随后,进行了两项实验来评估这两个区域在阿扑吗啡条件性上下文刺激后 ERK 的激活。在实验 1 中,大鼠在置于开阔场之前每天接受 5 次 2.0mg/kg 阿扑吗啡或载体注射。在两天的停药期后,进行了条件测试,其中大鼠接受了 30 分钟的非药物测试。测试完成后立即进行免疫组织化学方案以测量 ERK 激活。在实验 2 中,进行了类似的测试方案,只是在开阔场测试后 30 分钟给予治疗(试验后实验)。结果表明,在测试前给予重复的阿扑吗啡治疗会引起条件作用。在前额叶皮层中观察到 ERK 激活增加,但在伏隔核中则没有。在试验后实验中没有观察到条件反应,也没有差异 ERK 激活。这些观察结果表明,前额叶皮层参与了多巴胺刺激引起的联想神经适应性变化。