Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior
Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior
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DOI：
10.1038/npp.2016.157
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发表时间：
2017-02-01
影响因子：
7.6
通讯作者：
Fuchs, Rita A.
中科院分区：
文献类型：
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作者：
Arguello, Amy A.;Richardson, Ben D.;Fuchs, Rita A.
可卡因成瘾是一种疾病，其特征是尽管长时间戒断，但仍会慢性复发。外侧眶额皮质（IOFC）和基底外侧杏仁核（BLA）在对与药物相关的条件刺激（CS）作出反应时会促进寻求可卡因的行为，并且两者之间有密集的双向连接。因此，我们假设这些脑区之间的单突触投射介导了CS诱导的寻求可卡因的行为。
雄性斯普拉格 - 道利大鼠接受双侧注射一种表达与报告蛋白（NpHR - mCheny）融合的增强型盐细菌视紫红质3.0的Cre依赖性腺相关病毒（AAV）载体，或一种对照AAV（mCheny），并在IOFC（实验1）或BLA（实验2）植入光纤。相同的大鼠还接受双侧注射一种向BLA（实验1）或IOFC（实验2）逆行运输的表达Cre重组酶的AAV载体（Retro - Cre - GFP）。因此，在不同组中，NpHR - mCheny或mCheny的表达靶向投射到BLA的IOFC神经元或投射到IOFC的BLA神经元。
大鼠被训练通过按压杠杆来获取与5秒CS呈现配对的可卡因注射。然后反应被消退。在测试中，反应相依的CS呈现与光遗传学抑制（5秒激光激活）离散耦合或无光遗传学抑制，同时在没有可卡因/食物强化的情况下评估杠杆反应。与（i）无光遗传学抑制或（ii）mCheny对照组的操作或（iii）NpHR - mCheny食物对照组相比，在NpHR - mCherry组中对IOFC到BLA（而非BLA到IOFC）投射的光遗传学抑制破坏了CS诱导的寻求可卡因行为的恢复。这些发现表明，IOFC通过单突触连接向BLA发送必要的输入，以促进CS诱导的寻求可卡因的行为。
Cocaine addiction is a disease characterized by chronic relapse despite long periods of abstinence. The lateral orbitofrontal cortex (IOFC) and basolateral amygdala (BLA) promote cocaine-seeking behavior in response to drug-associated conditioned stimuli (CS) and share dense reciprocal connections. Hence, we hypothesized that monosynaptic projections between these brain regions mediate CS-induced cocaine-seeking behavior. Male Sprague-Dawley rats received bilateral infusions of a Cre-dependent adeno-associated viral (AAV) vector expressing enhanced halorhodopsin 3.0 fused with a reporter protein (NpHR-mCheny) or a control AAV (mCheny) plus optic fiber implants into the IOFC (Experiment I) or BLA (Experiment 2). The same rats also received bilateral infusions of a retrogradely transported AAV vector expressing Cre recombinase (Retro-Cre-GFP) into the BLA (Experiment I) or IOFC (Experiment 2). Thus, NpHR-mCheny or mCheny expression was targeted to IOFC neurons that project to the BLA or to BLA neurons that project to the IOFC in different groups. Rats were trained to lever press for cocaine infusions paired with 5-s CS presentations. Responding was then extinguished. At test, response-contingent CS presentation was discretely coupled with optogenetic inhibition (5-s laser activation) or no optogenetic inhibition while lever responding was assessed without cocaine/food reinforcement. Optogenetic inhibition of IOFC to BLA, but not BLA to IOFC, projections in the NpHR-mCherry groups disrupted CS-induced reinstatement of cocaine-seeking behavior relative to (i) no optogenetic inhibition or (ii) manipulations in mCheny control or (iii) NpHR-mCheny food control groups. These findings suggest that the IOFC sends requisite input to the BLA, via monosynaptic connections, to promote CS-induced cocaine-seeking behavior.