Objective To investigate whether environmental cues associated with different properties of morphine could regulate the extracellular levels of glutamate and y-aminobutyric acid （GABA） in the hippocampal ventral sub...Objective To investigate whether environmental cues associated with different properties of morphine could regulate the extracellular levels of glutamate and y-aminobutyric acid （GABA） in the hippocampal ventral subiculum, which play a critical role in the reinstatement of drug-seeking behavior induced by environmental cues. Methods Conditioning place preference （CPP） and conditioning place aversion （CPA） models were used to establish environment associated with rewarding and aversive properties of morphine respectively. Microdialysis and high performance liquid chromatography were used to measure the extracelluar level of glutamate and GABA in the ventral subiculum under these environmental cues. Results Exposure to the environmental cues associated with rewarding properties of morphine resulted in a decrease （approximately 11%） of extracellular level of GABA in ventral subiculum, and exposure to the environmental cues associated with aversive properties of morphine resulted in an increase （approximately 230%） of extracellular level of glutamate in ventral subiculum. Conclusion Environmental cues associated with different properties of morphine modulate the release of distinct neurotransmitters in the hippocampal ventral subiculum possibly through different neural circuit.展开更多
In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor （NMDAR） plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glyci...In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor （NMDAR） plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR respons- es induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca2＋ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subnnits in this effect. We found that the peak current of NMDARs and Ca2＋ influx induced by high concentration of NMDA were reduced by treatment of gly- cine （0.03-10 I.tmol L-1） in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L-1 NMDA, was reversed by ZnCI2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.展开更多
基金supported by the National Natural Science Foundation of China(No.30230130 and No.30400129)the Ministry of Science and Technology of China(No.2003CB515405,No.2005CB522406)+1 种基金the Program for Changjiang Scholars and Innovative Research Team of Ministry of Education of ChinaShanghai Municipal Commission for Science and Technology(No.06JC14008).
文摘Objective To investigate whether environmental cues associated with different properties of morphine could regulate the extracellular levels of glutamate and y-aminobutyric acid （GABA） in the hippocampal ventral subiculum, which play a critical role in the reinstatement of drug-seeking behavior induced by environmental cues. Methods Conditioning place preference （CPP） and conditioning place aversion （CPA） models were used to establish environment associated with rewarding and aversive properties of morphine respectively. Microdialysis and high performance liquid chromatography were used to measure the extracelluar level of glutamate and GABA in the ventral subiculum under these environmental cues. Results Exposure to the environmental cues associated with rewarding properties of morphine resulted in a decrease （approximately 11%） of extracellular level of GABA in ventral subiculum, and exposure to the environmental cues associated with aversive properties of morphine resulted in an increase （approximately 230%） of extracellular level of glutamate in ventral subiculum. Conclusion Environmental cues associated with different properties of morphine modulate the release of distinct neurotransmitters in the hippocampal ventral subiculum possibly through different neural circuit.
基金supported by the National Basic Research Program of China (Grant No. J20110170)the National Natural Science Foundation of China (Grant Nos. 81000497 and 81071614)
文摘In the presence of glutamate and co-agonists, e.g., glycine, the N-methyl-D-aspartate receptor （NMDAR） plays an important role in physiological and pathophysiological brain processes. Previous studies indicate glycine could inhibit NMDAR respons- es induced by high concentration of NMDA in hippocampal neurons. The mechanism underlying this inhibitory impact, how- ever, has been unclear. In this study, the whole-cell patch-clamp recording and Ca2＋ imaging with Fluo-3/AM under laser scanning confocal microscope were used to analyze the possible involvement of NMDAR subnnits in this effect. We found that the peak current of NMDARs and Ca2＋ influx induced by high concentration of NMDA were reduced by treatment of gly- cine （0.03-10 I.tmol L-1） in a dose-dependent manner, and that the glycine-dependent inhibition of NMDAR responses, which were induced at 300 mol L-1 NMDA, was reversed by ZnCI2 through the blocking of the NR2A subunit of NMDARs, but was less influenced by ifenprodil, a NR2B inhibitor. Our results suggest that the glycine-dependent inactivation of NMDARs is potentially modulated by the regulatory subunit NR2A.
