Maldonado-Irizarry C S, Swanson C J, Kelley A E
Department of Psychology, Northeastern University, Boston, Massachusetts 02114, USA.
J Neurosci. 1995 Oct;15(10):6779-88. doi: 10.1523/JNEUROSCI.15-10-06779.1995.
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" and "shell". 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.
伏隔核是大脑中一个在调节食欲行为和强化作用方面被认为很重要的区域。伏隔核接收来自皮质边缘和丘脑结构的传入输入，这些输入主要由兴奋性氨基酸（EAA）编码。本研究在伏隔核两个最近被确定的亚区域，即“核心”和“壳”中，研究了EAA输入到伏隔核在大鼠进食行为中的作用。在第一系列实验中，结果显示，在对应于内侧壳亚区域的伏隔核内侧部分阻断α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）和海人藻酸谷氨酸受体，会导致明显的进食反应。双侧微量注射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）后，立即以剂量依赖的方式显著刺激食物摄入。将DNQX注入对应于核心的伏隔核中央区域，并未引发进食。将NMDA拮抗剂2-氨基-5-膦酰戊酸（AP-5）和MK-801（马来酸氯胺酮）注入这两个区域均未引发进食。对DNQX的进食反应被局部共同注射AMPA所阻断。用纳曲酮（5毫克/千克）进行全身预处理对DNQX引发的进食反应没有影响；然而，事先全身给予D-1和D-2拮抗剂会使反应降低一半，这表明多巴胺在该反应中起调节作用。此外，通过同时向伏隔核壳的主要投射区域外侧下丘脑注入GABAA激动剂蝇蕈醇（10、25纳克），进食反应被完全抑制。这些发现证明了伏隔核壳中的非NMDA受体在摄食行为中具有选择性作用，并表明参与奖赏的两个主要脑区，即伏隔核和外侧下丘脑之间存在重要的功能联系。
