下丘脑神经肽Y缺失大鼠对神经肽Y的进食反应增强。

Enhanced feeding response to neuropeptide Y in hypothalamic neuropeptide Y-depleted rats.

作者信息

Stricker-Krongrad A, Beck B, Burlet C

机构信息

INSERM U-308, MRCA, Equipe de Neurobiologie et Physiologie Expérimentales, Nancy, France.

出版信息

Eur J Pharmacol. 1996 Jan 4;295(1):27-34. doi: 10.1016/0014-2999(95)00647-8.

DOI:10.1016/0014-2999(95)00647-8

PMID:8925871

Abstract

Monosodium glutamate is neurotoxic for the arcuate nucleus and more generally for all circumventricular organs when injected in newborn rats. Neuropeptide Y, a potent stimulator of food intake, is mainly synthesized in the arcuate nucleus. In the present experiment, we determined the hypothalamic status and the feeding response to intracerebroventricular neuropeptide Y in adult rats neonatally treated with monosodium glutamate. Marked neuropeptide Y decreases were measured in the arcuate nucleus and in the paraventricular nuclei in monosodium glutamate-treated rats (-40%; P < 0.01). Adult rats neonatally treated with monosodium glutamate weighed significantly less (-8%; P < 0.01) and ate less (-10%; P < 0.01) than the control rats. Neuropeptide Y injections in a lateral brain ventricle stimulated food intake in control and monosodium glutamate-treated rats in a dose-dependent manner (P < 0.001). Whatever the time after drug injection (2, 4, 6 and 8 h) and the injected dose (0.5, 1 and 5 micrograms), feeding responses were always greater in monosodium glutamate-treated rats (about 2 times greater starting with the lowest dose (0.5 microgram): 9.3 +/- 1.0 (monosodium glutamate) vs. 5.3 +/- 0.7 (control) g/2 h, P < 0.01). Calculated minimal effective doses were also always smaller in monosodium glutamate-treated rats than in control animals (P < 0.01). Neuropeptide Y increased meal duration, meal size and decreased latency to initiate feeding in monosodium glutamate-treated rats (P < 0.01) and control rats (P < 0.01). For each dose of neuropeptide Y, effects were more pronounced on meal size (+70%) and meal duration (+25%) in monosodium glutamate-treated rats than in control rats. Therefore, monosodium glutamate-treated rats were more sensitive to exogenous neuropeptide Y. Decreased food intake in the monosodium glutamate-treated rats was associated with a decrease in neuropeptide Y concentrations in the arcuate-paraventricular axis. This confirms the functional role of this peptidergic pathway in eating behavior.

摘要

在新生大鼠中注射味精时，味精对弓状核具有神经毒性，更普遍地说，对所有室周器官都有神经毒性。神经肽Y是一种强力的食物摄入刺激剂，主要在弓状核中合成。在本实验中，我们测定了新生期经味精处理的成年大鼠的下丘脑状态以及对脑室内注射神经肽Y的进食反应。在经味精处理的大鼠中，弓状核和室旁核中的神经肽Y显著减少（-40%；P < 0.01）。新生期经味精处理的成年大鼠体重显著较轻（-8%；P < 0.01），进食量也较少（-10%；P < 0.01），低于对照大鼠。向侧脑室注射神经肽Y以剂量依赖性方式刺激对照大鼠和经味精处理的大鼠的食物摄入（P < 0.001）。无论药物注射后的时间（2、4、6和8小时）以及注射剂量（0.5、1和5微克）如何，经味精处理的大鼠的进食反应总是更大（从最低剂量（0.5微克）开始约大2倍：9.3±1.0（经味精处理）对5.3±0.7（对照）克/2小时，P < 0.01）。经味精处理的大鼠计算出的最小有效剂量也总是比对照动物小（P < 0.01）。神经肽Y增加了经味精处理的大鼠（P < 0.01）和对照大鼠（P < 0.01）的进食持续时间、进食量，并减少了开始进食的潜伏期。对于每剂量的神经肽Y，经味精处理的大鼠对进食量（+70%）和进食持续时间（+25%）的影响比对对照大鼠更明显。因此，经味精处理的大鼠对外源性神经肽Y更敏感。经味精处理的大鼠食物摄入量减少与弓状核-室旁核轴中神经肽Y浓度降低有关。这证实了这条肽能通路在进食行为中的功能作用。