Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats
Involvement of AMPA/kainate, NMDA, and mGlu5 receptors in the nucleus accumbens core in cue-induced reinstatement of cocaine seeking in rats
复制标题
DOI：
10.1007/s00213-007-0753-8
复制
发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Hyytia, Petri
中科院分区：
文献类型：
--
作者：
Backstrom, Pia;Hyytia, Petri
目的研究α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）/红藻氨酸（KA）对大鼠药物依赖性行为的影响，并探讨其机制。N-甲基-D-天冬氨酸（NMDA）和mGlu 5受体阻断剂对提示性可卡因觅药的再诱发作用在FR 4（FR 5：S）二阶强化时间表下与药物（光和色调）接触。灭绝后，在此期间，既没有可卡因，也没有复合刺激，恢复响应由应急介绍的复合刺激。脑内AMPA/红藻氨酸受体拮抗剂6-氰基-7-硝基喹喔啉-2，3-二酮的作用（CNQX; 0、0.01和0.03 μ g/侧），NMDA拮抗剂D- 2-氨基-5-膦酰基戊酸（D-AP 5; 0、1和2 μ g/侧），和mGluR 5拮抗剂2-甲基-6-甲基-N-（2-甲基-N-氧代-N-甲基-N-氧代苯乙炔基吡啶（MPEP; 00.5结果CNQX和D-AP 5减弱了cue-1的表达，诱导可卡因寻求剂量依赖性的恢复。然而，MPEP仅相对于基线减少了可卡因寻求，因为包括在受试者内系列注射中的盐水媒介物也减少了响应，这可能反映了MPEP的条件性快感缺乏效应。在额外的实验中，没有拮抗剂衰减自发活动或响应蔗糖pellet.Conclusions的结果表明，线索诱导恢复可卡因寻求一段时间后，从可卡因是敏感的AMPA/红藻氨酸和NMDA受体拮抗剂在核cubens核心，并提供了进一步的证据的作用，在药物寻求行为的调制中的谷氨酸传输。
Rationale Nucleus accumbens glutamate transmission has been implicated in drug- seeking behavior, but the involvement of glutamate receptor subtypes in drug seeking maintained by drug- associated cues has not been fully investigated.Objective This study examined the effects of alpha- amino-3-hydroxy- 5-methyl- 4- isoxazolepropionic acid (AMPA)/ kainate, N-methyl-D- aspartate (NMDA) and mGlu5 receptor blockade in the nucleus accumbens core on cue- induced reinstatement of cocaine seeking.Method Wistar rats were trained to self-administer cocaine and associate a compound stimulus (light and tone) with the drug under an FR4(FR5: S) second- order schedule of reinforcement. After extinction, during which neither cocaine nor the compound stimulus was available, responding was reinstated by contingent presentations of the compound stimulus. The effects of the intra- accumbal AMPA/kainate receptor antagonist 6- cyano- 7-nitro-quinoxaline2, 3-dione (CNQX; 0, 0.01, and 0.03 mu g/ side), the NMDA antagonist D- 2-amino-5-phosphonopentanoate (D- AP5; 0, 1, and 2 mu g/ side), and the mGluR5 antagonist 2-methyl- 6-(phenylethynyl)- pyridine (MPEP; 0, 0.5, and 1 mu g/ side) on reinstatement were examined in a within-subjects design.Results CNQX and D-AP5 attenuated cue- induced reinstatement of cocaine seeking dose-dependently. MPEP, however, decreased cocaine seeking only relative to baseline because also the saline vehicle included in the within-subjects series of injections decreased responding, possibly reflecting conditioned anhedonic effects of MPEP. In additional experiments, none of the antagonists attenuated locomotor activity or responding for sucrose pellets.Conclusions The results suggest that cue- induced reinstatement of cocaine seeking after a period of withdrawal from cocaine is sensitive to AMPA/kainate and NMDA receptor antagonism in the nucleus accumbens core and give further evidence for the role of the accumbal glutamate transmission in modulation of drug-seeking behavior.