Taber M T, Fibiger H C
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Neuroscience. 1997 Feb;76(4):1105-12. doi: 10.1016/s0306-4522(96)00450-2.
The extent to which glutamate receptors in the nucleus accumbens and ventral tegmental area regulate feeding-evoked increases in dopamine release in the nucleus accumbens was determined using in vivo brain microdialysis in the rat. In some animals a second dialysis probe was implanted in the ventral tegmental area ipsilateral to the nucleus accumbens probe. The feeding protocol involved access to standard rat chow after 18 h of food deprivation. Under these conditions rats began eating approximately 30 s after the introduction of food and consumed 7-8 g, resulting in a 50% increase in dopamine release. Application of the glutamate receptor antagonist kynurenate (1 mM) in the nucleus accumbens potentiated the feeding-evoked increase in dopamine release by 80%. Application of the metabotropic glutamate receptor agonist trans-1S,3R-1-amino-1,3-cyclopentanedicarboxylic acid (100 microM) in the nucleus accumbens blocked the feeding-evoked increase in dopamine release. Application of a combination of the ionotropic glutamate receptor antagonists 2-amino-5-phosphopentanoic acid (200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) through the dialysis probe in the ventral tegmental area reduced basal dopamine output in the nucleus accumbens by 20% and markedly attenuated (by 70%) the effect of feeding on dopamine release. None of the treatments affected the latency to eat or the volume of food consumed. These results indicate that glutamatergic afferents to the ventral tegmental area mediate feeding-induced increases in dopamine release in the nucleus accumbens. In contrast, at physiological concentrations, glutamate in the nucleus accumbens appears to decrease dopamine release via actions on ionotropic and metabotropic receptors.
运用大鼠体内脑微透析技术，确定伏隔核和腹侧被盖区中的谷氨酸受体对进食诱发的伏隔核多巴胺释放增加的调节程度。在一些动物中，第二个透析探针被植入与伏隔核探针同侧的腹侧被盖区。进食方案包括在禁食18小时后给予标准大鼠饲料。在这些条件下，大鼠在引入食物后约30秒开始进食，消耗7 - 8克，导致多巴胺释放增加50%。在伏隔核中应用谷氨酸受体拮抗剂犬尿烯酸（1 mM）使进食诱发的多巴胺释放增加增强了80%。在伏隔核中应用代谢型谷氨酸受体激动剂反式-1S,3R-1-氨基-1,3-环戊烷二羧酸（100 microM）阻断了进食诱发的多巴胺释放增加。通过腹侧被盖区的透析探针应用离子型谷氨酸受体拮抗剂2-氨基-5-磷酸戊酸（200 microM）和6-氰基-7-硝基喹喔啉-2,3-二酮（50 microM）的组合，使伏隔核中的基础多巴胺输出降低了20%，并显著减弱（70%）了进食对多巴胺释放的影响。所有处理均未影响进食潜伏期或食物消耗量。这些结果表明，向腹侧被盖区的谷氨酸能传入神经介导了进食诱导的伏隔核多巴胺释放增加。相反，在生理浓度下，伏隔核中的谷氨酸似乎通过作用于离子型和代谢型受体来减少多巴胺释放。
