Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus
Glutamate receptors in the nucleus accumbens shell control feeding behavior via the lateral hypothalamus
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DOI：
10.1523/jneurosci.15-10-06779.1995
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发表时间：
1995-10
期刊：
影响因子：
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通讯作者：
CS Maldonado-Irizarry;CJ Swanson;A. Kelley
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文献类型：
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作者：
CS Maldonado-Irizarry;CJ Swanson;A. Kelley
食欲核：大脑中的一个区域，被认为在调节食欲行为和加强食欲方面起重要作用伏隔核接收来自皮质边缘和丘脑结构的传入输入，该输入主要由兴奋性氨基酸（EAA）编码。本研究调查了EAA输入到丘脑核在大鼠摄食行为中的作用，在丘脑的两个最近表征的亚区，“核”和“壳”中。在第一系列的实验中，它被证明，α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和红藻氨酸谷氨酸受体的阻断在内侧的部分，对应于内侧壳亚区，导致在一个显着的进食反应。双侧微量输注6，7-二硝基喹喔啉-2，3-二酮（DNQX，0.25-0.75微克/0.5微升）、6-氰基-7-硝基喹喔啉（CNQX，0.75-1.5微克）和2，3-二羟基-6-硝基-7-氨磺酰基苯并-（F）喹喔啉（NBQX，0.2-1.0微克）在输注后立即以剂量依赖性方式显著刺激摄食。输注DNQX到中央丘脑区域，对应于核心，没有引起喂养。输注NMDA拮抗剂2-氨基-5-磷酸戊酸（AP-5）和MK-801（马来酸地佐环平）在两个区域均未引起进食。DNQX的摄食反应可被AMPA阻断。用纳洛酮（5 mg/kg）进行全身预处理对DNQX喂养反应没有影响;然而，预先全身给予D-1和D-2拮抗剂使反应减少一半，表明多巴胺在反应中的调节作用。此外，进食反应被完全抑制的同时注入GABAA激动剂蝇蕈醇（10，25纳克）到外侧下丘脑，一个主要的投影面积的壳。这些研究结果表明，非NMDA受体在摄食行为的核壳的选择性作用，并提出了一个重要的功能之间的联系，两个主要的大脑区域参与奖励，核和外侧下丘脑。
The nucleus accumbens in a brain region considered to be important in the regulation of appetitive behavior and reinforcement. The accumbens receives afferent input from corticolimbic and thalamic structures, which is primarily coded by excitatory amino acids (EAAs). The present studies investigated the role of EAA input to the nucleus accumbens in feeding behavior in rats, in two recently characterized subregions of the accumbens, the “core#x201D; and #x201C;shell#x201D;. In the first series of experiments, it was shown that blockade of alpha-amino-3-hydroxy-5- methylisoxazole-4-propionic acid (AMPA) and kainate glutamate receptors in the medial part of the accumbens, corresponding to the medial shell subregion, resulted in a pronounced feeding response. Bilateral microinfusion of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.25–0.75 micrograms/0.5 microliters), 6-cyano-7-nitroquinoxaline (CNQX, 0.75–1.5 micrograms), and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo-(F) quinoxaline (NBQX, 0.2-1.0 micrograms) markedly stimulated food intake immediately following infusion, in a dose-dependent manner. Infusion of DNQX into the central accumbens region, corresponding to the core, did not elicit feeding. Infusion of the NMDA antagonists 2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 (dizocilpine maleate) did not elicit feeding in either region. The feeding response to DNQX was blocked by local coinfusion of AMPA. Systemic pretreatment with naltrexone (5 mg/kg) had no effect on the DNQX-feeding response; however, prior systemic administration of both D-1 and D-2 antagonists reduced the response by half, suggesting a modulatory role for dopamine in the response. Moreover, the feeding response was completely inhibited by concurrent infusion of the GABAA agonist muscimol (10, 25 ng) into the lateral hypothalamus, a major projection area of the accumbens shell. These findings demonstrate a selective role for non-NMDA receptors in the nucleus accumbens shell in ingestive behavior, and suggest an important functional link between two major brain regions involved in reward, the nucleus accumbens and lateral hypothalamus.