Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference,and delays morphine extinction in rats  

作　　者：Yaodong Fan Haichen Niu Joshua D. Rizak Ling Li Guimei Wang Liqi Xu He Ren Hao Lei Hualin Yu 

机构地区：[1]Department of Neurosurgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China [2]State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Math-ematics, Chinese Academy of Sciences, Wuhan 430071, China [3]State Key Laboratory of Brain and Cognitive Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China [4]Department of Medical Imaging, Kunming General Hospital of Chengdu Military Region, People's Liberation Army, Kunming 650032, China [5]Minimally Invasive Neurosurgery Department, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, China

出　　处：《Neuroscience Bulletin》2012年第5期567-576,共10页神经科学通报（英文版）

基　　金：supported by grants from the National Basic Research Development Program (973 Program) of China (2011CB707802,2011CB707800);the National Natural Science Foundation of China (81171302)

摘　　要：Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.Objective It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor （NMDAR）, play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 （GLT-1） （ceftriaxone） are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference （CPP） than either compound alone. Methods A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory （acquisition, extinction, and reinstatement of morphine preference） in rats. Results A low dose of neither MK-801 （0.05 mg/kg, i.p.） nor ceftriaxone （25 mg/kg, i.p.） alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. Conclusion The combined action of a low dose of an NMDAR antagonist （MK-801） and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

关 键 词：CEFTRIAXONE conditioned place preference MORPHINE MK-801 glutamate transporter subtype-1 

分 类 号：Q426[生物学—神经生物学] TU998[生物学—生理学]