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In summary, activation of frontal cortical D 4 R should mostly keep a low output signal of the PFC network ( 4 Rs localized in frontal cortico-striatal terminals to exert a significant inhibitory role of striatal glutamate release ( 4 Rs are instrumental for the dopamine-mediated functional inhibition of frontal cortico-striatal neurotransmission, in agreement with the hyperexcitability observed on frontal cortical P neurons in D 4 R-deficient mice ( 4 Rs can also directly mediate the effects of norepinephrine and indirectly modulate the function of adrenoceptors and other dopamine receptor subtypes by heteromerization