Doane Dolores F, Lawson Marcus A, Meade Jonathan R, Kotz Catherine M, Beverly J Lee
University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1022-6. doi: 10.1152/ajpregu.00282.2007. Epub 2007 May 30.
Food intake is stimulated following administration of orexin-A into the perifornical region of the lateral hypothalamus (LH/PFA). Orexin neurons originating in the LH/PFA interact with a number of hypothalamic systems known to influence food intake, including glutamatergic neurons. Glutamatergic systems in the LH/PFA were demonstrated to initiate feeding through N-methyl-d-aspartic acid (NMDA) receptors. Male Sprague-Dawley rats fitted with brain guide cannulas to the LH/PFA were used in two experiments. In the first experiment, a combination microdialysis/microinjection probe was used to deliver artificial cerebrospinal fluid (aCSF) or 500 pmol of orexin-A into the LH/PFA. Orexin-A increased interstitial glutamate to 143 +/- 12% of baseline (P < 0.05), which remained elevated over the 120-min collection period. In the second experiment, the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 10 nmol) was administered before orexin-A. The orexin-induced increase in food intake (from 1.1 +/- 0.4 to 3.2 +/- 0.5 g, P < 0.05) during the first hour was absent in rats receiving d-AP5 + orexin-A (1.2 +/- 0.5 g). There was no effect of d-AP5 alone on food intake. These data support glutamatergic systems in the LH/PFA mediating the feeding response to orexin-A through NMDA receptors.
在下丘脑外侧区穹窿周区域（LH/PFA）注射食欲素-A后，食物摄入量会增加。起源于LH/PFA的食欲素神经元与许多已知影响食物摄入的下丘脑系统相互作用，包括谷氨酸能神经元。LH/PFA中的谷氨酸能系统被证明可通过N-甲基-D-天冬氨酸（NMDA）受体引发进食。在两项实验中使用了装有通向LH/PFA的脑导向套管的雄性斯普拉格-道利大鼠。在第一个实验中，使用组合式微透析/微注射探针将人工脑脊液（aCSF）或500皮摩尔的食欲素-A注入LH/PFA。食欲素-A使间质谷氨酸水平升高至基线的143±12%（P<0.05），在120分钟的收集期内一直保持升高。在第二个实验中，在注射食欲素-A之前给予NMDA受体拮抗剂D-2-氨基-5-膦酰基戊酸（D-AP5；10纳摩尔）。在接受D-AP5+食欲素-A的大鼠中，在第一个小时内食欲素诱导的食物摄入量增加（从1.1±0.4克增加到3.±0.5克，P<0.05）并未出现（食物摄入量为1.2±0.5克）。单独使用D-AP5对食物摄入量没有影响。这些数据支持LH/PFA中的谷氨酸能系统通过NMDA受体介导对食欲素-A的进食反应。
