Howell Leonard L, Wilcox Kristin M
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Psychopharmacology (Berl). 2002 Oct;163(3-4):352-61. doi: 10.1007/s00213-002-1207-y. Epub 2002 Aug 29.
Recent advances in neuroimaging and in vivo neurochemistry have documented drug-induced functional changes in brain activity under physiologically relevant conditions. These approaches have significant strengths and important limitations that should be considered.
The present review describes current in vivo approaches to characterize drug effects as they relate to behavior, and highlights key contributions derived from each approach in the context of stimulant self-administration in primates.
Techniques relating in vitro neurochemistry to behavioral pharmacology are compared to several in vivo approaches, including microdialysis, positron emission tomography (PET) neuroimaging and functional magnetic resonance imaging (fMRI).
In vitro neurochemical correlates of behavioral pharmacology established a significant relationship between dopamine and the reinforcing effects of abused stimulants. Subsequent in vivo microdialysis studies in behaving animals supported a critical role for nucleus accumbens dopamine in the reinforcing effects of stimulants. PET neuroimaging in monkeys and humans documented a close relationship between dopamine transporter (DAT) occupancy in vivo and the reinforcing effects of stimulants. The effectiveness of selective DAT inhibitors to reduce cocaine self-administration also was linked to DAT occupancy in vivo. Lastly, the measurement of cerebral blood flow and metabolism with PET and fMRI has begun to define the neuronal circuitry influenced by acute and chronic stimulant exposure.
Collectively, in vivo neurochemistry and functional imaging have complemented in vitro approaches and have enhanced our current understanding of the neurobiology of abused stimulants.
神经影像学和体内神经化学的最新进展已证明，在生理相关条件下，药物会引起大脑活动的功能变化。这些方法有显著的优势和重要的局限性，均应予以考虑。
本综述描述了目前用于表征与行为相关的药物效应的体内研究方法，并强调了在灵长类动物兴奋剂自我给药的背景下，每种方法所做出的关键贡献。
将体外神经化学与行为药理学相关的技术与几种体内研究方法进行比较，包括微透析、正电子发射断层扫描（PET）神经成像和功能磁共振成像（fMRI）。
行为药理学的体外神经化学相关性确立了多巴胺与滥用兴奋剂的强化作用之间的显著关系。随后在行为动物中进行的体内微透析研究支持伏隔核多巴胺在兴奋剂强化作用中起关键作用。对猴子和人类的PET神经成像记录了体内多巴胺转运体（DAT）占有率与兴奋剂强化作用之间的密切关系。选择性DAT抑制剂减少可卡因自我给药的有效性也与体内DAT占有率有关。最后，利用PET和fMRI对脑血流量和代谢的测量已开始确定受急性和慢性兴奋剂暴露影响的神经回路。
总体而言，体内神经化学和功能成像补充了体外研究方法，并增进了我们目前对滥用兴奋剂神经生物学的理解。
