Interactions of the basolateral amygdala with the dorsal hippocampus and dorsomedial prefrontal cortex regulate drug context-induced reinstatement of cocaine-seeking in rats
Interactions of the basolateral amygdala with the dorsal hippocampus and dorsomedial prefrontal cortex regulate drug context-induced reinstatement of cocaine-seeking in rats
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DOI：
10.1111/j.1460-9568.2007.05674.x
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发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Bell, Guinevere H.
中科院分区：
文献类型：
--
作者：
Fuchs, Rita A.;Eaddy, Jessica L.;Bell, Guinevere H.
基底外侧杏仁核（BLA），背内侧前额叶皮层（dmPFC）和背侧海马（DH）的神经回路的药物上下文诱导恢复可卡因寻求的关键要素，然而，鲜为人知的是，这些大脑区域之间的功能相互作用。本研究测试的假设，串行信息处理的BLA和dmPFC介导的药物上下文诱导的可卡因寻求，而BLA和DH独立控制这种行为。训练大鼠在不同的环境中自我施用可卡因（可卡因配对背景），然后在不同的环境中进行灭绝训练（灭绝背景）。在试验日，大鼠接受巴氯芬+蝇蕈醇或载体单侧微量输注到BLA和对侧或同侧dmPFC或DH。可卡因寻求行为（即可卡因相关的杠杆上的非加强压力），然后在可卡因配对和灭绝的情况下进行评估。车辆预处理后，暴露于可卡因配对的上下文恢复熄灭可卡因寻求行为。BLA-dmPFC不对称失活衰减可卡因寻求行为相对于车辆处理，但是，这种损害等同于同侧BLA-dmPFC失活所产生的。此外，单侧失活的BLA或dmPFC没有改变这种行为。BLA-DH不对称失活选择性衰减可卡因寻求行为相对于车辆处理，而同侧或单侧失活的BLA和DH没有改变这种行为。这些发现表明，BLA和DH表现出连续的信息处理内复发电路。相比之下，BLA和dmPFC之间的相互作用更为复杂，包括信息处理的平行循环和/或从dmPFC到BLA的必要的半球间输入，可能除了直接的半球内相互作用。
The basolateral amygdala (BLA), dorsomedial prefrontal cortex (dmPFC) and dorsal hippocampus (DH) are critical elements of the neurocircuitry of drug context-induced reinstatement of cocaine-seeking; however, little is known about functional interactions between these brain regions. The present study tested the hypothesis that serial information processing by the BLA and dmPFC mediates drug context-induced cocaine-seeking, whereas the BLA and DH independently control this behaviour. Rats were trained to self-administer cocaine in a distinct environment (cocaine-paired context) followed by extinction training in a different environment (extinction context). On the test days, rats received unilateral microinfusions of baclofen + muscimol or of vehicle into the BLA and either the contralateral or ipsilateral dmPFC or DH. Cocaine-seeking behaviour (i.e. nonreinforced presses on the cocaine-associated lever) was then assessed in the cocaine-paired and extinction contexts. Following vehicle pretreatment, exposure to the cocaine-paired context reinstated extinguished cocaine-seeking behaviour. BLA-dmPFC asymmetrical inactivation attenuated cocaine-seeking behaviour relative to vehicle treatment; however, this impairment equaled that produced by ipsilateral BLA-dmPFC inactivation. Furthermore, unilateral inactivation of the BLA or dmPFC did not alter this behaviour. BLA-DH asymmetrical inactivation selectively attenuated cocaine-seeking behaviour relative to vehicle treatment whereas ipsilateral or unilateral inactivation of the BLA and DH did not alter this behaviour. These findings indicate that the BLA and DH exhibit sequential information processing within the relapse circuitry. In contrast, interactions between the BLA and dmPFC are more complex and include parallel loops of information processing and/or necessary interhemispheric input from the dmPFC to the BLA, probably in addition to direct intrahemispheric interactions.