Phillips G D, Le Noury J, Wolterink G, Donselaar-Wolterink I, Robbins T W, Everitt B J
Department of Anatomy, University of Cambridge, UK.
Behav Brain Res. 1993 Jun 30;55(2):223-31. doi: 10.1016/0166-4328(93)90118-a.
Cholecystokinin (CCK) is colocalised with dopamine in the postero-medial nucleus accumbens (NAS). We have utilised an acquisition of a new response procedure to investigate the interaction between CCK and dopamine in the control over behaviour by conditioned reinforcers. A conditioned reinforcer (CR) may be defined as an initially neutral stimulus which gains control over behaviour through selective association with a primary reinforcer. Here, rats learned to associate a light/noise compound stimulus with the imminent availability of 10% sucrose reinforcement. Later, in the absence of sucrose, responding on one of two novel levers (the CR lever) was acquired and maintained by contingent presentation of the CR alone, while responding on the second lever had no programmed consequences. In Expt. 1, infusion of 10 micrograms D-amphetamine within the postero-medial NAS enhanced responding selectively on the CR lever. Infusion of sulphated CCK octapeptide (CCK: 1 or 10 ng) alone within the same area had no effect on response rate. However, infusion of CCK immediately prior to D-amphetamine caused a dose-dependent potentiation of the impact of D-amphetamine upon rates of response on the CR lever. In Expt. 2, infusion of D-amphetamine (10 micrograms) within the postero-medial NAS again enhanced responding selectively upon the CR lever. Intra-accumbens infusion of CCK (10 ng), or s.c. administration of the CCKA receptor antagonist devazepide had no effect upon response rates. However, CCK again potentiated the D-amphetamine-induced increase in rates of response, and this potentiation was blocked by pretreatment with devazepide. These results are discussed in terms of the co-modulation by CCK and dopamine of the processing of reward-related stimuli within the NAS.
胆囊收缩素（CCK）与多巴胺共同存在于伏隔核后内侧核（NAS）中。我们采用了一种新的反应程序习得方法来研究CCK和多巴胺在条件强化物对行为的控制过程中的相互作用。条件强化物（CR）可定义为一种最初中性的刺激，它通过与初级强化物的选择性关联来获得对行为的控制。在此，大鼠学会将光/噪声复合刺激与即将可得的10%蔗糖强化物联系起来。之后，在没有蔗糖的情况下，通过单独呈现CR来获得并维持在两个新杠杆之一（CR杠杆）上的反应，而在第二个杠杆上的反应没有设定的结果。在实验1中，向NAS后内侧注入10微克D-苯丙胺可选择性增强在CR杠杆上的反应。在同一区域单独注入硫酸化CCK八肽（CCK：1或10纳克）对反应率没有影响。然而，在注入D-苯丙胺之前立即注入CCK会导致D-苯丙胺对CR杠杆反应率的影响出现剂量依赖性增强。在实验2中，向NAS后内侧注入D-苯丙胺（10微克）再次选择性增强了在CR杠杆上的反应。向伏隔核内注入CCK（10纳克）或皮下注射CCKA受体拮抗剂地伐西匹对反应率没有影响。然而，CCK再次增强了D-苯丙胺诱导的反应率增加，并且这种增强被地伐西匹预处理所阻断。将根据CCK和多巴胺对NAS内与奖励相关刺激的处理的共同调节来讨论这些结果。
