Cocaine-cue extinction training combined with brief interventions of environmental enrichment (EE) was shown previously to facilitate extinction and attenuate reacquisition of cocaine self-administration in rats. It is unknown whether or not the usefulness of this approach would be undermined if extinction training took place in a novel rather than familiar context. Drawing on previous studies involving pharmacological interventions, we hypothesized that the facilitative effects of EE for cocaine relapse prevention would be independent of the context used for extinction training. Rats trained to self-administer cocaine underwent cocaine-cue extinction training in either the familiar self-administration context or a novel context, with or without EE. Rats then were tested for reacquisition of cocaine self-administration in the familiar context. Target brain regions were lysed and probed for memory-related changes in receptors for glutamate and BDNF by western blotting. Contrary to our hypothesis, the facilitative effects of EE for cocaine relapse prevention were dependent on the context used for extinction training. While EE facilitated extinction regardless of context used, it inhibited cocaine relapse only after extinction training in the familiar context. EE was associated with increased GluA2 in nucleus accumbens, TrkB in dorsal hippocampus and activated TrkB in ventromedial prefrontal cortex. Of these, the changes in dorsal hippocampus and ventromedial prefrontal cortex mirrored outcomes of the cocaine relapse tests in that these changes were specific to rats receiving EE plus extinction training in the familiar context. These findings support a role for hippocampal-prefrontal BDNF-TrkB signaling in extinction-based relapse prevention strategies involving EE.

中文翻译：

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环境丰富对可卡因复发预防的促进作用取决于灭绝训练环境，并涉及背海马和腹内侧前额叶皮层中增加的 TrkB 信号。

可卡因提示灭绝训练与环境富集 (EE) 的简短干预相结合，先前已显示可促进灭绝并减少大鼠对可卡因自我给药的重新获得。如果灭绝训练发生在新颖而不是熟悉的环境中，这种方法的实用性是否会受到损害尚不清楚。借鉴以前涉及药物干预的研究，我们假设 EE 对可卡因复发预防的促进作用将与用于灭绝训练的背景无关。接受过自我给药可卡因训练的大鼠在熟悉的自我给药环境或新环境中接受可卡因提示灭绝训练，有或没有 EE。然后在熟悉的环境中测试大鼠重新获得可卡因自我给药。裂解靶脑区域并通过蛋白质印迹探测谷氨酸和 BDNF 受体的记忆相关变化。与我们的假设相反，EE 对可卡因复发预防的促进作用取决于用于灭绝训练的背景。虽然 EE 促进了灭绝，而不管使用的环境如何，它只有在熟悉的环境中进行灭绝训练后才能抑制可卡因复发。EE 与伏隔核中 GluA2 增加、背海马中 TrkB 和腹内侧前额叶皮层中激活的 TrkB 相关。其中，背海马体和腹内侧前额叶皮层的变化反映了可卡因复发测试的结果，因为这些变化是在熟悉的环境中接受 EE 加灭绝训练的大鼠所特有的。