Stanley B G, Willett V L, Donias H W, Dee M G, Duva M A
Department of Neuroscience, University of California, Riverside 92521, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):R443-9. doi: 10.1152/ajpregu.1996.270.2.R443.
To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.
为了确定内源性下丘脑外侧区（LH）谷氨酸及其N-甲基-D-天冬氨酸（NMDA）受体是否可能参与对自然进食的刺激，我们在成年雄性大鼠中测试了向LH注射NMDA拮抗剂D-（-）-2-氨基-5-磷酸戊酸（D-AP5）对以下因素引起的进食的抑制作用：1）向LH注射NMDA、海藻酸或D，L-α-氨基-3-羟基-5-甲基异恶唑（AMPA）；2）食物剥夺；3）夜间时段开始。D-AP5（10 - 100 nmol）使NMDA（10 nmol）引起的约10克进食反应减少了72 - 90%，而不影响海藻酸（1.0 nmol）或AMPA（1.0 nmol）引起的数量相似的进食反应。这种处理还使剥夺诱导的进食最多减少61%，夜间进食最多减少40%。为了确定其长期影响，每天两次向LH双侧注射D-AP5（50 nmol），连续注射8天。这种处理导致每日食物摄入量最多减少65%，体重减轻最多达13克/天。这些结果表明D-AP5对进食和体重有行为学上的选择性抑制作用，这表明内源性LH谷氨酸起到调节自然进食和体重的作用，并且NMDA受体参与这些功能。
