Kramar Cecilia P, Barbano M Flavia, Medina Jorge H
Instituto de Biología Celular y Neurociencias (CONICET-UBA), Facultad de Medicina, UBA, Buenos Aires, Argentina.
Instituto de Biología Celular y Neurociencias (CONICET-UBA), Facultad de Medicina, UBA, Buenos Aires, Argentina; National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, MD, USA.
Neurobiol Learn Mem. 2014 Dec;116:172-80. doi: 10.1016/j.nlm.2014.10.004. Epub 2014 Oct 30.
The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories.
海马体在支持情境与非条件刺激之间的联想学习的记忆中的作用已得到充分证明。海马体多巴胺神经传递调节恐惧驱动和空间学习任务的突触可塑性和记忆处理。关于海马体及其D1/D5多巴胺受体在药物相关经历记忆的获取、巩固和表达中的参与情况，尤其是在单次配对可卡因条件性位置偏爱（CPP）训练的处理过程中，人们了解得要少得多。为了确定可卡因CPP记忆形成的时间动态，我们在单配对CPP范式中训练大鼠，并在条件作用后的不同时间间隔对它们进行测试。与可卡因相关的记忆持续24小时但不是72小时。然后，我们在不同阶段向双侧背侧海马体注入GABAA受体激动剂蝇蕈醇或D1/D5多巴胺受体拮抗剂SCH 23390，以评估参与可卡因CPP记忆获取、巩固或表达的机制。训练时阻断D1/D5多巴胺受体会损害可卡因CPP记忆的获取，在训练后立即或12小时给药时没有任何影响。在测试时给予SCH 23390也会影响可卡因CPP记忆的表达。相反地，蝇蕈醇仅在条件作用后12小时给药时会损害可卡因CPP记忆的巩固。这些发现表明，背侧海马体的多巴胺能输入对于单次试验可卡因相关记忆的获取和表达是必需的，而该结构的神经活动对于这类记忆的晚期巩固是必需的。
