Hajnal Andras, Acharya Nikhil K, Grigson Patricia S, Covasa Mihai, Twining Robert C
Dept. of Neural and Behavioral Sciences H181, College of Medicine, Pennsylvania State University, Hershey, PA 17033, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Nov;293(5):R1846-54. doi: 10.1152/ajpregu.00461.2007. Epub 2007 Sep 5.
CCK-1-receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and exhibit a greater preference for sucrose compared with lean controls [Long-Evans Tokushima Otsuka (LETO)]. To directly assess motivation to work for sucrose reward in this model of obesity and type 2 diabetes, we examined the operant performance of OLETF rats at nondiabetic and prediabetic stages (14 and 24 wk of age, respectively) on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. To evaluate the involvement of dopamine systems, the effects of the D1 receptor antagonist SCH23390 (100 and 200 nmol/kg ip) and the D2 receptor antagonist raclopride (200 and 400 nmol/kg ip), were also tested on PR responding for sucrose. Compared with age-matched LETO rats, 14-wk-old OLETF rats emitted more licks on the "active" empty spout operant on the FR-10 schedule of reinforcement to obtain 0.01 M and 0.3 M sucrose and completed higher ratio requirements on the PR schedule to gain access to 0.3 M and 1.0 M sucrose. At 24 wk, this effect was limited to 1.0 M sucrose. Both antagonists were potent in reducing operant responding to 0.3 M sucrose in both strains at both ages, and there was no strain effect to SCH23390 at either age. OLETF rats, on the other hand, showed an increased sensitivity to the higher dose of raclopride, resulting in reduced responding to sucrose reinforcement at 24 wk. Taken together, these findings provide the first direct evidence for an increased motivation for sucrose reward in the OLETF rats and suggest altered D2 receptor regulation with the progression of obesity and prediabetes.
胆囊收缩素-1受体缺陷型大冢长- Evans德岛肥胖（OLETF）大鼠食量过大，与瘦型对照大鼠[大冢长- Evans德岛（LETO）大鼠]相比，对蔗糖的偏好更强。为了在这种肥胖和2型糖尿病模型中直接评估为获得蔗糖奖励而工作的动机，我们研究了OLETF大鼠在非糖尿病和糖尿病前期阶段（分别为14周龄和24周龄）在固定比率（FR）和累进比率（PR）强化程序下的操作性行为表现。为了评估多巴胺系统的参与情况，还测试了D1受体拮抗剂SCH23390（100和200 nmol/kg腹腔注射）和D2受体拮抗剂雷氯必利（200和400 nmol/kg腹腔注射）对PR程序中蔗糖反应的影响。与年龄匹配的LETO大鼠相比，14周龄的OLETF大鼠在FR - 10强化程序的“活动”空喷嘴操作性任务中，为获得0.01 M和0.3 M蔗糖而发出的舔舐次数更多，并且在PR程序中为获得0.3 M和1.0 M蔗糖而完成的比率要求更高。在24周时，这种效应仅限于1.0 M蔗糖。两种拮抗剂在两个年龄阶段对两个品系中0.3 M蔗糖的操作性反应均有显著抑制作用，且在两个年龄阶段对SCH23390均无品系效应。另一方面，OLETF大鼠对较高剂量的雷氯必利表现出更高的敏感性，导致在24周时对蔗糖强化的反应减少。综上所述，这些发现首次直接证明了OLETF大鼠对蔗糖奖励的动机增加，并表明随着肥胖和糖尿病前期的进展，D2受体调节发生了改变。
