Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, CCNE, Universidade Federal de Santa Maria, CEP 97105-900, Santa Maria, RS, Brazil.
Neurobiol Learn Mem. 2012 Mar;97(3):294-300. doi: 10.1016/j.nlm.2012.02.002. Epub 2012 Feb 27.
Previous exposure to the training context disrupts glutamatergic N-methyl-d-aspartate receptor (NMDAr) antagonist-induced amnesia, indicating that novelty is necessary for such an amnestic effect. While there are reports that novelty-related release of opioids cause amnesia, no study has addressed whether the amnestic effect of NMDAr antagonists involve opioid mechanisms. In this study we investigated whether pharmacological manipulation of the opioid system immediately after context pre-exposure alters the amnestic effect of arcaine, a NMDAr antagonist. Adult male Wistar rats were habituated (pre-exposed) to a fear conditioning training apparatus or to a different context (open field). Immediately after pre-exposure, animals were injected with saline or naloxone (0.5 mg/kg, i.p.) or anti-beta-endorphin antibody (1:500, i.c.v.). Forty eight hours after pre-exposure session, all animals were subjected to fear conditioning acquisition protocol and saline or arcaine (30 mg/kg, i.p.) was administered immediately after training. Testing was carried out 24 h later, and freezing responses due to re-exposure to the training apparatus were recorded. Pre-exposure to the training apparatus prevented the impairment of memory induced by post-training arcaine. Administration of naloxone or anti-beta-endorphin antibody, immediately after pre-exposure to the training apparatus, reinstated the amnesic effect of post-training arcaine. The results suggest that endogenous opioid mechanisms are involved in the pre-exposure-induced loss of the amnestic effect of arcaine.
先前暴露于训练环境会破坏谷氨酸 N-甲基-D-天冬氨酸受体（NMDAr）拮抗剂引起的健忘症，表明新颖性是产生这种健忘效应的必要条件。虽然有报道称与新颖性相关的阿片类物质释放会导致健忘症，但没有研究探讨 NMDAr 拮抗剂的健忘效应是否涉及阿片类机制。在这项研究中，我们研究了在上下文预暴露后立即对阿片系统进行药理学操作是否会改变 NMDAr 拮抗剂烟酰胺的健忘效应。成年雄性 Wistar 大鼠习惯于（预先暴露）恐惧条件反射训练装置或不同的环境（开阔场地）。在预暴露后立即，动物接受生理盐水或纳洛酮（0.5mg/kg，ip）或抗β-内啡肽抗体（1:500，icv）注射。预暴露后 48 小时，所有动物都接受了恐惧条件反射获得协议，并且在训练后立即给予生理盐水或烟酰胺（30mg/kg，ip）。24 小时后进行测试，并记录由于重新暴露于训练装置而产生的冻结反应。对训练装置的预先暴露可防止记忆因训练后烟酰胺引起的损害。在训练前立即给予纳洛酮或抗β-内啡肽抗体可恢复训练后烟酰胺引起的健忘作用。结果表明，内源性阿片类机制参与了预暴露诱导的烟酰胺健忘效应的丧失。
