Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala.
Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala.
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DOI：
10.1523/jneurosci.6165-09.2010
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发表时间：
2010-03-31
期刊：
影响因子：
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通讯作者：
Meredith GE
中科院分区：
文献类型：
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作者：
Rademacher DJ;Rosenkranz JA;Morshedi MM;Sullivan EM;Meredith GE
当个体暴露于具有吸毒的感官线索的环境时，就会出现寻求毒品和复发的脆弱性。记忆的形成被认为需要突触回路的可塑性，因此我们研究了药物配对环境的记忆是否与基底外侧杏仁核（BLA）突触回路的变化相关，其中情绪学习是一种公认的现象。在条件性位置偏爱实验中，我们使用安非他明（AMPH）作为非条件刺激。用1.0 mg/kg AMPH调节大鼠，并在最后一次调节后72 h进行无药物测试。对照组包括生理盐水调节组和家庭笼AMPH注射组，其暴露于CPP装置延迟4 h，足够长的时间以从脑中清除AMPH。采用电镜和体视学设计方法对BLA内的兴奋性突触进行计数。与对照组相比，表达AMPH CPP的大鼠兴奋性突触增加。兴奋性突触活动的测定使用在体内的细胞内记录从BLA在麻醉大鼠。我们发现，AMPH CPP，但不是单独的药物，增加突触驱动的措施，包括突触事件的频率，和成对脉冲比的突触输入BLA锥体神经元。在体研究结果表明，BLA神经元兴奋性驱动的增加反映了兴奋性突触数量的变化。因此，背景药物协会伴随着BLA的结构和功能可塑性，研究结果对药物寻求行为具有重要意义。
Drug seeking and the vulnerability to relapse occur when individuals are exposed to an environment with sensory cues where drug taking has occurred. Memory formation is thought to require plasticity in synaptic circuits, and so we examined whether the memory for a drug-paired environment correlates with changes in the synaptic circuits of the basolateral amygdala (BLA), where emotional learning is a recognized phenomenon. We used amphetamine (AMPH) as the unconditioned stimulus in the conditioned place preference (CPP) paradigm. Rats were conditioned with 1.0 mg/kg AMPH and tested, drug-free, 72 h after the last conditioning session. Controls included a saline conditioned group and a home cage AMPH injection group, whose exposure to the CPP apparatus was delayed by 4 h, long enough to clear the AMPH from the brain. We counted excitatory synapses in the BLA using the electron microscope and the physical disector design (stereology). Rats that expressed AMPH CPP had an increase in excitatory synapses compared to controls. Excitatory synaptic activity was measured using in vivo intracellular recordings from the BLA in anesthetized rats. We found that AMPH CPP, but not drug alone, increased measures of synaptic drive, including the frequency of synaptic events, and the paired-pulse ratio of synaptic inputs to BLA pyramidal neurons. The in vivo findings suggest that the increase in BLA neuronal excitatory drive reflects the change in excitatory synapse number. Thus, context-drug associations are accompanied by structural and functional plasticity in the BLA, findings that have important implications for drug-seeking behavior.