Dissociating anorexia and anhedonia elicited by interleukin-1β:: antidepressant and gender effects on responding for "free chow" and "earned" sucrose intake
Dissociating anorexia and anhedonia elicited by interleukin-1β:: antidepressant and gender effects on responding for "free chow" and "earned" sucrose intake
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DOI：
10.1007/s00213-002-1273-1
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发表时间：
2003-02-01
影响因子：
3.4
通讯作者：
Anisman, H
中科院分区：
文献类型：
--
作者：
Merali, Z;Brennan, K;Anisman, H
理论基础：细胞因子是免疫系统的信号分子，与抑郁症的诱因有关。分析白细胞介素1β(IL-1β)的行为效应及其抗抑郁药物的修饰是复杂的，因为细胞因子的厌食症和厌食症效应不容易彼此分离。目的：研究IL-1β在雄性和雌性大鼠自由进食实验食物和按累进比率(PR)程序对蔗糖奖励的反应方面的作用。这个时间表通过逐步增加老鼠必须花费的努力来评估回应的动机，以获得固定的奖励。使用这个时间表，就有可能评估慢性氟西汀在减弱IL-1β效应方面的影响。方法：在一次腹腔注射IL-1β治疗的大鼠中，评估被训练为按公关程序反应蔗糖奖励的大鼠，以及那些可以获得即席食物的大鼠。在第二个实验中，大鼠长期灌胃给予氟西汀30天，然后评估IL-1β的作用。结果：单次注射IL-1β可减少雄性和雌性大鼠48h的摄食量，而雄性大鼠获得蔗糖奖赏的努力在24 h内减少，而雌性大鼠持续72 h，长期给予氟西汀可减轻IL-1β引起的PR表现障碍，但不改变减少的摄食量。结论：(A)IL-1β的厌食和厌食效应是分离的，(B)细胞因子干扰动机，(C)抗抑郁治疗优先影响IL-1β的厌食效应。
Rationale: Cytokines, signaling molecules of the immune system, have been implicated in the provocation of depression. Analysis of the behavioral effects of interleukin-1beta (IL-1beta), and their modification by antidepressants, is complicated since the anorexic and anhedonic effects of the cytokine-are not readily dissociated from one another. Objectives: The effects of IL-1beta in male and female rats were evaluated with respect to free consumption of lab chow and responding for sucrose reward on a progressive ratio (PR) schedule. This schedule assesses motivation to respond by progressively increasing the efforts rats must expend to receive a fixed reward. Using this schedule, it was then possible to assess the influence of chronic fluoxetine in attenuating the effects of IL-1beta. Methods: The effect of a single intraperitoneal injection of IL-1beta treatment was assessed in rats trained to respond on a PR schedule for sucrose reward, and who could obtain ad lib chow. In a second experiment rats were pretreated chronically with fluoxetine by gavage for 30 days, after which the effects of IL-1beta were assessed. Results: A single intraperitoneal injection of IL-1beta reduced chow consumption for 48 h in both males and females; in contrast, among males, the effort expended to gain sucrose reward was reduced for 24 h, while in females the effect persisted for 72 h. Chronic pretreatment with fluoxetine attenuated the disturbance of PR performance elicited by IL-1beta, but did not alter the reduced chow consumption. Conclusions: It is suggested that (a) the anhedonic and anorexic effects of IL-1beta are dissociable, (b) the cytokine disturbs incentive motivation, and (c) antidepressant treatment preferentially influences the anhedonic effects elicited by IL-1beta.