Repeated amphetamine administration induces Fos in prefrontal cortical neurons that project to the lateral hypothalamus but not the nucleus accumbens or basolateral amygdala
Repeated amphetamine administration induces Fos in prefrontal cortical neurons that project to the lateral hypothalamus but not the nucleus accumbens or basolateral amygdala
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DOI：
10.1007/s00213-007-1021-7
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Meredith, Gloria E.
中科院分区：
文献类型：
--
作者：
Morshedi, Maud M.;Meredith, Gloria E.
原理：对安非他明（AMPH）致敏的发展依赖于从内侧前额叶皮层（mPFC）到皮层下中心的兴奋性流出的增加。这些预测对于药物给药期间持续到停药期间的行为反应的逐步增强显然是重要的。本研究的目的是确定mPFC皮层下通路被AMPH增敏方案激活。材料和方法采用逆行标记技术，研究了致敏大鼠注射AMPH后mPFC主要投射通路中Fos的激活情况。结果反复注射AMPH的大鼠mPFC、伏隔核（NAc）、杏仁核基底外侧（BLA）和下丘脑外侧（LH）的fos免疫反应细胞明显高于对照。反复AMPH处理后，投射到LH而非NAc或BLA的mPFC锥体神经元表现出显著的Fos诱导。此外，我们发现fos激活的食欲素神经元显著增加。LH是一个参与自然和药物奖励过程的区域，可能通过其与mPFC的连接，并可能通过其食欲素神经元，在重复AMPH致敏的发展和持续中发挥作用。
Rationale The development of sensitization to amphetamine (AMPH) is dependent on increases in excitatory outflow from the medial prefrontal cortex (mPFC) to subcortical centers. These projections are clearly important for the progressive enhancement of the behavioral response during drug administration that persists through withdrawal.Objectives The objective of this study was to identify the mPFC subcortical pathway(s) activated by a sensitizing regimen of AMPH.Materials and methods Using retrograde labeling techniques, Fos activation was evaluated in the predominant projection pathways of the mPFC of sensitized rats after a challenge injection of AMPH.Results There was a significant increase in Fos-immunoreactive cells in the mPFC, nucleus accumbens (NAc), basolateral amygdala (BLA), and lateral hypothalamus (LH) of rats treated repeatedly with AMPH when compared to vehicle-treated controls. The mPFC pyramidal neurons that project to the LH but not the NAc or BLA show a significant induction of Fos after repeated AMPH treatment. In addition, we found a dramatic increase in Fos-activated orexin neurons.Conclusions The LH, a region implicated in natural and drug reward processes, may play a role in the development and persistence of sensitization to repeated AMPH through its connections with the mPFC and possibly through its orexin neurons.