DOPAMINE D1 AND N-METHYL-D-ASPARTATE RECEPTORS AND EXTRACELLULAR SIGNAL-REGULATED KINASE MEDIATE NEURONAL MORPHOLOGICAL CHANGES INDUCED BY REPEATED COCAINE ADMINISTRATION

作者：Ren Z; Sun W L; Jiao H; Zhang D; Kong H; Wang X; Xu M^*

来源：Neuroscience, 2010, 168(1): 48-60.

DOI：10.1016/j.neuroscience.2010.03.034

• D1 and D2 receptors
• NMDA receptors
• ERK
• cocaine
• dendrite
• spine density

The development of drug addiction involves persistent cellular and molecular changes in the CNS. The brain dopamine and glutamate systems play key roles in mediating drug-induced neuroadaptation. Changes in dendritic morphology in medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and caudate putamen (CPu) accompany drug-induced enduring behavioral and molecular changes. We have investigated the potential involvement of dopamine D1 and D2 receptors, the N-methyl-D-aspartate (NMDA) receptor, and the extracellular signal-regulated kinase (ERK) in dendritic morphological changes induced by repeated cocaine administration. We show that either a genetic mutation or pharmacological blockade of dopamine D1 receptors attenuated cocaine-induced changes in both dendritic branching and spine density of MSNs in the shell of the NAc and CPu. In contrast, antagonism of dopamine D2 receptors had no obvious effect on changes in dendritic branching but had a partial effect on changes in spine density of MSNs in these brain regions following repeated cocaine injections. Pharmacological inhibition of either NMDA receptors or ERK attenuated cocaine-induced changes in both dendritic branching and spine density of MSNs in the shell of the NAc and CPu. These results suggest that dopamine D1 and NMDA receptors and ERK contribute significantly to neuronal morphological changes induced by repeated exposure to cocaine.

• 出版日期2010-6-16