Giorgi O, Piras G, Lecca D, Corda M G
Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Neuroscience. 2005;135(3):987-98. doi: 10.1016/j.neuroscience.2005.06.075. Epub 2005 Sep 8.
The selectively bred Roman high- and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naïve rats) and after the repeated administration of amphetamine (1 mg/kg, s.c. x 10 days) or saline. We show that (1) in naïve rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman high-avoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated dopaminergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman low-avoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction.
经过选择性培育的罗马高回避型和低回避型大鼠在情绪以及对急性和反复给予精神兴奋剂的运动效应的反应性方面存在差异。这些品系在其边缘中脑多巴胺系统对成瘾药物的神经化学反应上也表现出巨大差异。伏隔核在精神兴奋剂产生的运动激活以及反复给药后观察到的这种效应增强（即行为敏化）中起关键作用，尽管对于伏隔核核心或伏隔核壳是否优先参与此类改变尚无普遍共识。本研究旨在评估急性给予苯丙胺（0.20 mg/kg，皮下注射）对基础条件下（即未处理大鼠）以及反复给予苯丙胺（1 mg/kg，皮下注射×10天）或生理盐水后的罗马品系大鼠伏隔核壳和伏隔核核心中多巴胺释放的影响。我们发现：（1）在未处理大鼠中，仅在罗马高回避型品系中，苯丙胺导致伏隔核壳中多巴胺释放的增加幅度大于伏隔核核心；（2）反复给予苯丙胺可使罗马高回避型大鼠而非罗马低回避型大鼠产生行为敏化；（3）与反复给予生理盐水的罗马高回避型大鼠相比，在致敏的罗马高回避型大鼠中，苯丙胺引起伏隔核核心中多巴胺释放的更大增加以及伏隔核壳中多巴胺能反应的减弱；（4）在对敏化有抗性的罗马低回避型品系的中脑伏隔核多巴胺能系统中未观察到此类神经化学变化。我们提出：（1）罗马高回避型和罗马低回避型大鼠在发展精神兴奋剂敏化的易感性方面存在差异；（2）伏隔核核心和伏隔核壳在这一现象中发挥不同的功能作用；（3）对罗马品系的比较研究可能有助于深入了解神经底物和遗传背景对个体成瘾易感性的影响。
