Sokolowski J D, Salamone J D
Department of Psychology, University of Connecticut, Storrs 06269-1020, USA.
Pharmacol Biochem Behav. 1998 Mar;59(3):557-66. doi: 10.1016/s0091-3057(97)00544-3.
Three experiments investigated the behavioral effects of injections of the neurotoxic agent 6-hydroxydopamine (6-OHDA) into the core or shell of the nucleus accumbens. In the first experiment, it was observed that injections of 6-OHDA into either core or shell had no significant effect on variable interval 30-s responding. In Experiment 2, responding on a fixed ratio 5 (FR5) schedule was impaired by 6-OHDA injections in the core, but not the shell. Rats with core injections of 6-OHDA showed significant alterations in the relative distribution of interresponse times, which were indicative of reductions in the maximal rate of responding and increases in the number of pauses. In the third experiment, rats were tested using a lever-pressing/chow-feeding procedure, in which a preferred food (Bioserve pellets) was available by pressing a lever on a FR5 schedule, but a less preferred food (lab chow) was also available concurrently in the test chamber. Untreated rats usually pressed the lever at high rates to obtain the food pellets and ate little of the lab chow. After training, dopamine depletions were produced by injections of 6-OHDA directly into the core or dorsomedial shell subregions. Injections of 6-OHDA into the core significantly decreased lever pressing for food pellets, increased lab chow consumption, and decreased the relative amount of food obtained by lever pressing. Dorsomedial shell injections of 6-OHDA had no significant effects on either lever pressing or lab chow consumption. Neurochemical results indicate that injections of 6-OHDA in the shell produced substantial depletions in the shell that were somewhat selective; however, injections of 6-OHDA into the core tended to deplete both core and shell. Correlational analyses revealed that decreases in FR5 lever pressing were associated with dopamine levels in the core, but not the shell. The present results indicate that substantial depletions of dopamine in the dorsomedial shell are not sufficient for suppressing reinforced lever pressing, and indicate that dopamine depletions must include the core area to impair performance on these tasks. The lack of effect of accumbens dopamine depletions on VI30 responding are consistent with the notion that accumbens dopamine depletions affect responding on schedules that generate a high rate of responding (FR5), but not those that generate a moderate rate of responding (e.g., VI30 s). The results of the concurrent FR5/chow-feeding experiment indicate that rats with accumbens dopamine depletions remain directed towards the acquisition and consumption of food. These results suggest that dopamine in the core region of accumbens sets constraints upon the selection of food-related behaviors, and that core dopamine depletions alter the relative allocation of food-related responses.
三项实验研究了向伏隔核核心或壳部注射神经毒性剂6-羟基多巴胺（6-OHDA）的行为效应。在第一个实验中，观察到向核心或壳部注射6-OHDA对30秒可变间隔反应没有显著影响。在实验2中，核心部位注射6-OHDA会损害固定比率5（FR5）程序的反应，但壳部注射则不会。核心注射6-OHDA的大鼠在反应间隔时间的相对分布上出现了显著变化，这表明最大反应速率降低，停顿次数增加。在第三个实验中，使用杠杆按压/进食程序对大鼠进行测试，在该程序中，通过按FR5程序的杠杆可获得一种偏好食物（Bioserve颗粒），但在测试箱中同时也可获得一种不太偏好的食物（实验室饲料）。未处理的大鼠通常以高频率按压杠杆以获取食物颗粒，而很少吃实验室饲料。训练后，通过直接向核心或背内侧壳部亚区域注射6-OHDA产生多巴胺耗竭。向核心注射6-OHDA显著减少了对食物颗粒的杠杆按压，增加了实验室饲料的消耗量，并减少了通过杠杆按压获得的食物的相对量。背内侧壳部注射6-OHDA对杠杆按压或实验室饲料消耗均无显著影响。神经化学结果表明，壳部注射6-OHDA在壳部产生了大量耗竭，且具有一定的选择性；然而，向核心注射6-OHDA往往会使核心和壳部均出现耗竭。相关分析显示，FR5杠杆按压的减少与核心部位的多巴胺水平相关，而与壳部无关。目前的结果表明，背内侧壳部多巴胺的大量耗竭不足以抑制强化的杠杆按压，这表明多巴胺耗竭必须包括核心区域才能损害这些任务的表现。伏隔核多巴胺耗竭对VI30反应没有影响，这与伏隔核多巴胺耗竭影响产生高反应率（FR5）的程序的反应，但不影响产生中等反应率（如VI30秒）的程序的反应这一观点一致。同时进行的FR5/进食实验结果表明，伏隔核多巴胺耗竭的大鼠仍然倾向于获取和消耗食物。这些结果表明，伏隔核核心区域的多巴胺对与食物相关行为的选择设置了限制，核心多巴胺耗竭改变了与食物相关反应的相对分配。
