NMDA Receptor Hypofunction in the Prelimbic Cortex Increases Sensitivity to the Rewarding Properties of Opiates via Dopaminergic and Amygdalar Substrates

被引：43

作者：

Bishop, Stephanie F. ^{[1
]}

Lauzon, Nicole M. ^{[1
]}

Bechard, Melanie ^{[1
]}

Gholizadeh, Shervin ^{[1
]}

Laviolette, Steven R. ^{[1
]}

机构：

[1] Univ Western Ontario, Schulich Sch Med, Dept Anat & Cell Biol, London, ON N5Y 5T8, Canada

来源：

CEREBRAL CORTEX | 2011年 / 21卷 / 01期

基金：

加拿大健康研究院;

关键词：

addiction; dopamine; glutamate; memory; morphine; NMDA receptor; prefrontal cortex; VENTRAL TEGMENTAL AREA; MEDIAL PREFRONTAL CORTEX; METHYL-D-ASPARTATE; FREELY MOVING RAT; NUCLEUS-ACCUMBENS; HEROIN-SEEKING; EXTRACELLULAR CONCENTRATIONS; INDUCED REINSTATEMENT; PHYSICAL-DEPENDENCE; CONDITIONED HEROIN;

D O I：

10.1093/cercor/bhq060

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The medial prefrontal cortex (mPFC) plays a significant role in associative learning and memory formation during the opiate addiction process. Various lines of evidence demonstrate that glutamatergic (GLUT) transmission through the N-methyl D-aspartate (NMDA) receptor can modulate neuronal network activity within the mPFC and influence dopaminergic signaling within the mesocorticolimbic pathway. However, little is known about how modulation of NMDA receptor signaling within the mPFC may regulate associative opiate reward learning and memory formation. Using a conditioned place preference (CPP) procedure, we examined the effects of selective NMDA receptor blockade directly within the prelimbic cortex (PLC) during the acquisition of associative opiate reward learning. NMDA receptor blockade specifically within the PLC caused a strong potentiation in the rewarding effects of either systemic or intra-ventral tegmental area (intra-VTA) morphine administration. This reward potentiation was dose dependently blocked by coadministration of dopamine D1 or D2 receptor antagonists and by blockade of presynaptic GLUT release. In addition, pharmacological inactivation of the basolateral amygdala (BLA) also prevented intra-PLC NMDA receptor blockade-induced potentiation of opiate reward signals, demonstrating a functional interaction between inputs from the VTA and BLA within the PLC, during the encoding and modulation of associative opiate reward information.

引用

页码：68 / 80

页数：13

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