Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602, RJ, Brazil.
Department of Entomology and Plant Pathology, State University of North Fluminense Darcy Ribeiro, Campos dos Goytacazes, RJ, Brazil.
Behav Brain Res. 2019 Jun 3;365:56-65. doi: 10.1016/j.bbr.2019.02.022. Epub 2019 Feb 16.
Increases in medial prefrontal cortex ERK have been linked to learning and memory processes. In the present study separate groups of rats initially underwent testing in an open-field paired with either 2.0 mg/kg apomorphine or vehicle injections. Subsequently, in a brief conditioning 5 min. test the paired apomorphine group manifested a conditioned hyperactivity response. The vehicle/apomorphine groups were then subdivided into two vehicle and two apomorphine subgroups matched for their activity scores in this conditioning test. Following another apomorphine/vehicle pairing in the test environment the groups received 3 additional 5 min. non-drug conditioning tests in which the groups received post-trial vehicle/apomorphine treatments. The vehicle groups received vehicle either immediately or 15 min. after the first two of the three conditioning tests and the apomorphine groups received 2.0 mg/kg either immediately or 15 min. after the first two of the three conditioning tests. In the first conditioning test both of the apomorphine groups exhibited equivalent conditioned responses. By the third test, the conditioned response of the immediate post-trial apomorphine group remained robust whereas conditioned response of the 15 min. apomorphine post-trial group was extinguished. Immediately following the third conditioning test, the animals were euthanized and ERK was measured in the medial prefrontal cortex and the nucleus accumbens. ERK was enhanced in both brain areas, selectively in the immediate apomorphine post-trial group. Increased ERK activity linked to the presence of the apomorphine conditioned response coupled with the absence of increased ERK activity following extinction of the apomorphine conditioned response suggests that ERK activity immediately following a conditioning test is an indicator of activity in brain systems with substantial dopaminergic input that are important in learning and memory. The facilitative effects of the immediate post-trial apomorphine treatment on the conditioned response are also consistent with the proposition that immediate post-trial dopaminergic drug treatments can modify the re-consolidation of conditioned behavior.
内侧前额叶皮层 ERK 的增加与学习和记忆过程有关。在本研究中，单独的大鼠组最初在开放场中进行测试，同时接受 2.0mg/kg 阿扑吗啡或载体注射。随后，在一个短暂的条件 5 分钟。测试中，配对的阿扑吗啡组表现出条件性过度活跃反应。然后，将载体/阿扑吗啡组分为两组，每组在该条件测试中的活动评分相匹配。在测试环境中再次进行阿扑吗啡/载体配对后，两组接受另外三个 5 分钟的非药物条件测试，其中组接受试验后载体/阿扑吗啡治疗。载体组在第一次两个条件测试中的两个测试中立即或 15 分钟后接受载体，而阿扑吗啡组在第一次三个条件测试中的两个测试中立即或 15 分钟后接受 2.0mg/kg 阿扑吗啡。在第一次条件测试中，两个阿扑吗啡组均表现出等效的条件反应。到第三次测试时，立即进行试验后阿扑吗啡组的条件反应仍然很强，而 15 分钟后进行试验后阿扑吗啡组的条件反应则被消除。在第三次条件测试后立即，处死动物并测量内侧前额叶皮层和伏隔核中的 ERK。ERK 在两个脑区均增强，仅在立即进行试验后阿扑吗啡组中增强。与阿扑吗啡条件反应的存在相关的 ERK 活性增加，以及阿扑吗啡条件反应消退后 ERK 活性增加的缺失表明，条件测试后立即的 ERK 活性是大脑系统中多巴胺能输入的重要指标，这些系统在学习和记忆中很重要。立即进行试验后阿扑吗啡治疗对条件反应的促进作用也与立即进行试验后多巴胺药物治疗可以改变条件行为的再巩固的观点一致。
