Integrative Neuroscience Section, Integrative Neuroscience Branch, National Institutes of Health/National Institute on Drug Abuse/Intramural Research Program, Baltimore, MD 21224, USA.
Neuropsychopharmacology. 2011 Sep;36(10):2018-29. doi: 10.1038/npp.2011.89. Epub 2011 Jun 1.
Basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) interactions have been implicated in cue-elicited craving and drug seeking. However, the neurochemical mechanisms underlying drug/environment associations are ill-defined. We used in vivo microdialysis and pharmacological inactivation techniques to identify alterations in mPFC glutamate (GLU) and gamma-aminobutyric acid (GABA) transmission in response to cues previously associated with experimenter-administered cocaine (COC) and the BLA contribution to these effects. Rats received alternate day injections of COC and saline (SAL) paired with a distinct environment for 6 days. Behavioral, neurochemical and immunohistochemical studies were conducted, in drug-free animals, 24 h after the last conditioning session. Animals exposed to a COC-paired environment demonstrated an augmented locomotor activity (LMA) relative to those exposed to the SAL-paired environment. mPFC GABA neurotransmission in the COC-paired environment was significantly increased, whereas GLU overflow was unaltered. Dual labeling of cFos and glutamic acid decarboxylase 67 immunoreactivity in mPFC neurons revealed significantly greater colocalization of these proteins following exposure to the COC-associated environment (CAE) relative to pseudo-conditioned rats or rats exposed to the SAL-associated environment indicating that the conditioned neurochemical response to the COC-paired environment is associated with activation of intrinsic mPFC GABA neurons. BLA inactivation prevented the increase in LMA and the augmentation of mPFC GABA transmission produced by cue exposure. Intra-mPFC application of the AMPA/KA receptor antagonist, NBQX, produced similar effects. These findings indicate that exposure to a CAE increases mPFC GABA transmission by enhancing excitatory drive from the BLA and activation of AMPA/KA receptors on mPFC GABA neurons.
外侧杏仁核 (BLA) 和内侧前额叶皮层 (mPFC) 的相互作用与线索诱发的渴望和药物寻求有关。然而，药物/环境关联的神经化学机制尚未明确。我们使用体内微透析和药理学失活技术来确定先前与实验者给予可卡因 (COC) 相关的线索以及 BLA 对这些效应的贡献对 mPFC 谷氨酸 (GLU) 和γ-氨基丁酸 (GABA) 传递的影响。大鼠接受 COC 和盐水 (SAL) 的隔日注射，并与独特的环境配对，共进行 6 天。在最后一次条件作用后 24 小时，在无药物的动物中进行行为、神经化学和免疫组织化学研究。暴露于 COC 配对环境的动物表现出相对于暴露于 SAL 配对环境的动物更高的运动活性 (LMA)。COC 配对环境中的 mPFC GABA 神经传递显著增加，而 GLU 溢出未改变。mPFC 神经元中 cFos 和谷氨酸脱羧酶 67 免疫反应性的双重标记显示，暴露于 COC 相关环境 (CAE) 后这些蛋白质的共定位显著增加，而与假条件大鼠或暴露于 SAL 相关环境的大鼠相比，这表明对 COC 配对环境的条件性神经化学反应与 mPFC GABA 神经元的内在激活有关。BLA 失活阻止了线索暴露引起的 LMA 增加和 mPFC GABA 传递的增强。向 mPFC 内应用 AMPA/KA 受体拮抗剂 NBQX 也产生了类似的效果。这些发现表明，暴露于 CAE 通过增强来自 BLA 的兴奋性驱动以及激活 mPFC GABA 神经元上的 AMPA/KA 受体来增加 mPFC GABA 传递。
