大脑对人体生理状态的交互感受反馈在指导动机行为中起着重要作用。例如,负能量平衡状态倾向于增加探索性/寻求食物的行为,同时减少回避行为。我们最近报道,夜间食物剥夺减少了雄性(但不是雌性)大鼠的条件性被动回避行为。由于禁食会增加ghrelin的循环水平,我们假设ghrelin信号有助于禁食减少条件性回避的能力。为了测试这个,随意喂养的雄性大鼠使用轻度脚部电击进行被动回避训练。稍后,在一夜之间食物匮乏之后,相同的大鼠在回避试验前30分钟接受生长素释放肽受体拮抗剂(GRA)或生理盐水载体预处理.通过进入潜伏期和在休克配对环境中花费的时间来衡量,GRA恢复了禁食大鼠的被动回避。此外,与注射赋形剂的禁食大鼠相比,在再次暴露于休克配对环境之前接受GRA的禁食大鼠在孤立道的尾核中显示出更多的催乳素释放肽(PrRP)阳性去甲肾上腺素能(NA)神经元的cFos激活,伴随着PrRP神经元下游靶部位更多的cfos激活(即,下丘脑终末纹床核和室旁核)。这些结果支持ghrelin信号传导有助于禁食对学习的被动回避行为的抑制作用的观点。也许是通过抑制PrRP阳性NA神经元及其下游下丘脑和边缘前脑靶标的募集。
Interoceptive feedback to the brain regarding the body\'s physiological state plays an important role in guiding motivated behaviors. For example, a state of negative energy balance tends to increase exploratory/food-seeking behaviors while reducing avoidance behaviors. We recently reported that overnight food deprivation reduces conditioned passive avoidance behavior in male (but not female) rats. Since fasting increases circulating levels of ghrelin, we hypothesized that ghrelin signaling contributes to the ability of fasting to reduce conditioned avoidance.
Ad libitum-fed male rats were trained in a passive avoidance procedure using mild footshock. Later, following overnight food deprivation, the same rats were pretreated with ghrelin receptor antagonist (GRA) or saline vehicle 30 min before avoidance testing.
GRA restored passive avoidance in fasted rats as measured by both latency to enter and time spent in the shock-paired context. In addition, compared to vehicle-injected fasted rats, fasted rats that received GRA before reexposure to the shock-paired context displayed more cFos activation of prolactin-releasing peptide (PrRP)-positive noradrenergic (NA) neurons in the caudal nucleus of the solitary tract, accompanied by more cFos activation in downstream target sites of PrRP neurons (i.e., bed nucleus of the stria terminalis and paraventricular nucleus of the hypothalamus).
These results support the view that ghrelin signaling contributes to the inhibitory effect of fasting on learned passive avoidance behavior, perhaps by suppressing recruitment of PrRP-positive NA neurons and their downstream hypothalamic and limbic forebrain targets.