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Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors

By Calcium, Christine Konradi, Jean-christophe Leveque and Steven E. Hyman


Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D 1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur at the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find tha

Year: 2013
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