Parkinson J A, Olmstead M C, Burns L H, Robbins T W, Everitt B J
Department of Experimental Psychology, University of Cambridge, Cambridge, United Kingdom CB2 3EB.
J Neurosci. 1999 Mar 15;19(6):2401-11. doi: 10.1523/JNEUROSCI.19-06-02401.1999.
Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.
伏隔核(NAcc)内的多巴胺释放与滥用药物的奖赏和运动兴奋作用均有关联。研究了NAcc核心区和壳区在介导苯丙胺增强的条件性强化和运动方面的功能。最初训练大鼠将中性刺激(巴甫洛夫条件刺激,CS)与食物强化(非条件刺激,US)联系起来。在选择性破坏NAcc核心区或壳区的兴奋性毒性损伤后,动物接受额外的CS-US训练,然后测试它们对产生作为条件性强化物(CR)的CS的新工具性反应的习得情况。在每次训练前,向动物的NAcc内注射D-苯丙胺(0、1、3、10或20微克)。壳区损伤既不影响巴甫洛夫条件反射也不影响工具性条件反射,但完全消除了NAcc内注射苯丙胺对CR反应的增强作用。核心区损伤的动物在巴甫洛夫再训练期间表现受损,但在习得CR反应方面没有缺陷。然而,刺激诱导的CR杠杆反应的选择性降低,因为NAcc内注射苯丙胺剂量依赖性地增加了CR杠杆和非强化(对照)杠杆上的反应。壳区损伤导致活动减少,并减弱了苯丙胺诱导的活动。相反,核心区损伤导致活动亢进,并增强了苯丙胺的运动兴奋作用。这些结果表明NAcc亚区存在功能分离;壳区是NAcc内注射苯丙胺后增强CR反应和运动的刺激作用的关键部位,而核心区与CS-US关联表达的机制有关。