Bednar I, Qian M, Qureshi G A, Källström L, Johnson A E, Carrer H, Södersten P
Department of Clinical Neuroscience, Karolinska Institute, Huddinge, Sweden.
J Neuroendocrinol. 1994 Aug;6(4):403-8. doi: 10.1111/j.1365-2826.1994.tb00600.x.
Male rats treated with reserpine were motionless and ingested only a few of ten consecutive intraoral injections of a 1 M solution of sucrose. While injection of apomorphine, a dopamine agonist, stimulated locomotion and stereotyped sniffing in reserpinized rats, it did not reactivate ingestive responses. The non-competitive N-methyl-D-aspartate receptor antagonist MK801, however, stimulated locomotion as well as ingestion suggesting involvement of glutamate in the suppressive effect of resperpine on ingestive responses. A series of experiments was therefore undertaken to investigate the possible physiological role of glutamate in feeding. For this purpose, we used Grill's intraoral intake test, in which the rat is infused intraorally with a sucrose solution and the amount ingested measured. In untreated rats, MK801 dose-dependently facilitated ingestion of the sucrose solution and antagonized inhibition of ingestion by cholecystokinin octapeptide. Administration of cholecystokinin octapeptide or ingestion of sucrose increased the concentration of glutamate in the nucleus of the solitary tract, a brain stem relay transmitting sensory information from the gastrointestinal tract to the forebrain. MK801 was found to bind specifically to this brain area and block the elevation of glutamate and dopamine levels which occurred after treatment with cholecystokinin octapeptide in this neural site. Together these data suggest that dopamine and glutamate may interact within the nucleus of the solitary tract in controlling ingestive behaviour.
用利血平处理的雄性大鼠一动不动，在连续十次经口注射1 M蔗糖溶液时只摄入了少量。虽然注射多巴胺激动剂阿扑吗啡可刺激利血平化大鼠的运动和刻板嗅探，但它并未重新激活摄食反应。然而，非竞争性N-甲基-D-天冬氨酸受体拮抗剂MK801却能刺激运动和摄食，这表明谷氨酸参与了利血平对摄食反应的抑制作用。因此，我们进行了一系列实验来研究谷氨酸在进食过程中可能的生理作用。为此，我们采用了格里尔经口摄入试验，即给大鼠经口输注蔗糖溶液并测量其摄入量。在未处理的大鼠中，MK801剂量依赖性地促进了蔗糖溶液的摄入，并拮抗了八肽胆囊收缩素对摄食的抑制作用。给予八肽胆囊收缩素或摄入蔗糖会增加孤束核中谷氨酸的浓度，孤束核是一个脑干中继站，将来自胃肠道的感觉信息传递到前脑。发现MK801能特异性结合该脑区，并阻断八肽胆囊收缩素处理后该神经部位谷氨酸和多巴胺水平的升高。这些数据共同表明，多巴胺和谷氨酸可能在孤束核内相互作用以控制摄食行为。
