Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon.
Hippocampus. 2018 Mar;28(3):226-238. doi: 10.1002/hipo.22826. Epub 2018 Feb 2.
A key aspect of substance abuse is that drug taking often occurs in a specific context. As a consequence, exposure to drug-associated contexts can trigger cravings and relapse, even after long periods of abstinence. Although many studies have demonstrated that the hippocampus is critical for developing and retrieving contextual and spatial memories, comparatively little is known about the role of the hippocampus in acquiring and inhibiting memories involving contexts and drugs of abuse. We examined the effects of hippocampal inactivation on expression of cocaine-induced conditioned place preference (CPP) after initial acquisition or extinction of CPP in C57BL/6 mice. During acquisition of CPP, distinct tactile cues were paired with cocaine (20 mg kg , intraperitoneal, CS+) and different tactile cues were paired with saline (CS-) on alternate days. Groups differed in whether the CS+ and CS- cues were presented in the same large space (one-compartment procedure) or distinct small spaces (two-compartment procedure), as previous findings demonstrate that a two-compartment configuration facilitates acquisition and attenuates extinction of a cocaine-induced CPP. Microinjection of the GABA agonist, muscimol, into the dorsal hippocampus impaired (1) retrieval of a place preference after acquisition, (2) extinction of a place preference, and (3) retrieval of extinction. These effects differed depending on the spatial configuration during acquisition or extinction, suggesting that the dorsal hippocampus may differentially modulate drug seeking during retrieval and extinction of CPP.
药物滥用的一个关键方面是,药物的使用往往发生在特定的环境中。因此,即使在长时间的禁欲后,接触与药物相关的环境也会引发渴望和复发。尽管许多研究表明海马体对于发展和检索上下文和空间记忆至关重要,但对于海马体在获取和抑制涉及上下文和滥用药物的记忆方面的作用知之甚少。我们研究了海马体失活对 C57BL/6 小鼠在获得或消除可卡因诱导的条件性位置偏好(CPP)后的表达的影响。在 CPP 的获得过程中,不同的触觉线索与可卡因(20 mg/kg,腹腔内,CS+)配对,而不同的触觉线索与盐水(CS-)配对,每天交替进行。各组的区别在于 CS+和 CS-线索是在同一个大空间(一室程序)还是不同的小空间(两室程序)中呈现,因为之前的研究结果表明,两室配置有利于可卡因诱导的 CPP 的获得和减弱消退。将 GABA 激动剂 muscimol 微注射到海马体背侧会损害:(1)获得后对位置偏好的检索,(2)对位置偏好的消退,以及(3)对消退的检索。这些影响取决于获得或消退期间的空间配置,表明背侧海马体可能在 CPP 的检索和消退期间对药物寻求产生不同的调节作用。