Hedou G, Homberg J, Feldon J, Heidbreder C A
The Swiss Federal Institute of Technology Zürich (ETH), Laboratory of Behavioral Biology, Zürich, Switzerland.
Neuropharmacology. 2001 Mar;40(3):366-82. doi: 10.1016/s0028-3908(00)00174-x.
The present study investigated the effect of acute and repeated administrations of amphetamine (AMPH) on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the two main cytoarchitectonic subterritories of the medial prefrontal cortex (mPFC) (anterior cingulate and dorsocaudal prelimbic cortices vs ventral prelimbic and rostral infralimbic cortices). Both the acute locomotor effects of AMPH and the expression of behavioral sensitization following its repeated administration were also simultaneously assessed. The repeated, intermittent administration of AMPH over five consecutive days led to a significant sensitized locomotor response to a subsequent challenge that occurred following a 48-h withdrawal period. Basal dialysate DA levels were higher in the ventral mPFC compared with its dorsal counterpart in naive animals, that is prior to the acute administration of AMPH. However, the inverse relationship was observed in animals that had developed sensitization: basal dialysate DA levels were significantly lower in the ventral mPFC compared with the dorsal mPFC. In naïve animals, AMPH produced a significant decrease in DA levels in both the ventral and dorsal subregions of the mPFC. However, the inverse relationship was observed in animals that had developed sensitization: dialysate DA levels in response to AMPH remained significantly decreased in the dorsal mPFC, whereas DA went back to baseline levels in the ventral mPFC. Given that a critical concentration of DA is required for normal function of the mPFC, our results suggest that AMPH-induced changes in DA levels in different subregions of the mPFC are critical for both the acute effects of the drug and the expression of behavioral sensitization to its repeated administration by producing either less or more selectivity or sharpening of stimuli to cortico-cortical dendrites and subcortical synaptic afferents to the pyramidal cells located in the dorso-ventral axis of the mPFC.
本研究调查了急性和重复给予苯丙胺（AMPH）对内侧前额叶皮质（mPFC）两个主要细胞构筑亚区（前扣带回和背尾侧边缘前皮质与腹侧边缘前皮质和吻侧下边缘皮质）中多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC）、高香草酸（HVA）和5-羟吲哚乙酸（5-HIAA）的影响。同时还评估了AMPH的急性运动效应及其重复给药后行为敏化的表现。连续五天重复、间歇性给予AMPH导致对随后在48小时戒断期后发生的挑战产生显著的运动敏化反应。在未给药的动物（即急性给予AMPH之前）中，腹侧mPFC的基础透析液DA水平高于背侧mPFC。然而，在已产生敏化的动物中观察到相反的关系：与背侧mPFC相比，腹侧mPFC的基础透析液DA水平显著降低。在未给药的动物中，AMPH使mPFC腹侧和背侧亚区的DA水平显著降低。然而，在已产生敏化的动物中观察到相反的关系：背侧mPFC中对AMPH反应的透析液DA水平仍显著降低，而腹侧mPFC中的DA恢复到基线水平。鉴于mPFC的正常功能需要临界浓度的DA，我们的结果表明，AMPH诱导的mPFC不同亚区DA水平变化对于药物的急性效应以及对其重复给药的行为敏化表现至关重要，这是通过对位于mPFC背腹轴上的锥体细胞的皮质-皮质树突和皮质下突触传入产生或多或少的选择性或增强刺激来实现的。
