Lecca Daniele, Piras Giovanna, Driscoll Peter, Giorgi Osvaldo, Corda Maria G
Department of Toxicology, University of Cagliari, Via Ospedale, 72, 09124 Cagliari, Italy.
Neuropharmacology. 2004 Apr;46(5):688-99. doi: 10.1016/j.neuropharm.2003.11.011.
Addictive substances like morphine and psychostimulants induce a preferential increase in dopamine (DA) output in the nucleus accumbens (NAC), a major terminal field of the mesolimbic dopaminergic projection. Two subregions of the NAC, the dorsolateral core and the ventromedial shell, are thought to subserve different functions related to the reinforcing properties of natural and drug rewards. The selective breeding of Roman high- (RHA) and low-avoidance (RLA) rats, respectively, for rapid vs. extremely poor active avoidance acquisition in a shuttle-box has resulted in two phenotypes that differ in their behavioural and neurochemical responses to addictive drugs. We used brain dialysis to assess whether such differences in the responsiveness to drugs of abuse are related to differences in mesolimbic DA neuron function. In RHA rats, morphine, cocaine, and amphetamine caused a larger increase in DA efflux in the NAC shell vs. the NAC core, whereas the profile for the drug-induced increases in DA output was almost completely superimposable in the NAC shell and NAC core of RLA rats. Moreover, morphine, cocaine, and amphetamine caused a larger increment in basal DA output in the NAC shell of RHA rats vs. the NAC shell of RLA rats. These drugs also elicited a more robust increase in locomotion, rearing, sniffing, and grooming in RHA than in RLA rats. These results demonstrate that genetically determined differences in the functional properties of DA neurons projecting to the NAC shell may critically influence the behavioural response patterns to addictive drugs that distinguish the Roman lines.
吗啡和精神兴奋剂等成瘾性物质会优先增加伏隔核（NAC）中的多巴胺（DA）输出，伏隔核是中脑边缘多巴胺能投射的主要终末场。NAC的两个亚区，即背外侧核心区和腹内侧壳区，被认为分别承担与天然和药物奖赏强化特性相关的不同功能。通过在穿梭箱中分别对罗马高回避（RHA）和低回避（RLA）大鼠进行快速与极差主动回避习得的选择性育种，产生了两种在对成瘾药物的行为和神经化学反应上存在差异的表型。我们使用脑微透析来评估对滥用药物反应性的这种差异是否与中脑边缘DA神经元功能的差异有关。在RHA大鼠中，吗啡、可卡因和苯丙胺导致NAC壳区的DA流出量相比NAC核心区有更大增加，而在RLA大鼠的NAC壳区和NAC核心区，药物诱导的DA输出增加情况几乎完全重叠。此外，与RLA大鼠的NAC壳区相比，吗啡、可卡因和苯丙胺导致RHA大鼠的NAC壳区基础DA输出有更大增加。这些药物在RHA大鼠中引发的运动、竖毛、嗅探和理毛增加也比RLA大鼠更强烈。这些结果表明，投射到NAC壳区的DA神经元功能特性的基因决定差异可能会严重影响区分罗马品系的对成瘾药物的行为反应模式。
