コカイン関連キューに関わる前頭前野と側坐核ドーパミンの異なる役割

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  • Distinct role of dopamine in the PFC and NAc during exposure to cocaine-associated cues

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<p>The role of dopamine in the recognition of drug-associated environmental stimuli, retrieval of drug-associated memory and drug-seeking behaviors is not fully understood. Roles of dopamine neurotransmission in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in the cocaine conditioned place preference (CPP) paradigm were evaluated using in vivo microdialysis. In mice that had acquired cocaine CPP, dopamine levels in the PFC, but not in the NAc, increased in response to cocaine-associated cues when mice were placed in the cocaine-chamber of the two-separated chambers. The induction of the dopamine response and the development of cocaine CPP were mediated through activation of glutamate NMDA/AMPA receptor signaling in the PFC during conditioning. Activation of dopamine D1 or D2 receptor signaling in the PFC was required for cocaine-induced locomotion, but not for the induction of the dopamine response or the development of cocaine CPP. Interestingly, dopamine levels in the NAc increased in response to cocaine-associated cues when mice were placed at the center of the two-connected chambers, which requires motivated exploration associated with cocaine reward. Dopamine neurotransmission in the PFC is activated by the exposure to the cocaine-associated cues, whereas dopamine neurotransmission in the NAc is activated in the process of motivated exploration of cues associated with cocaine reward. Furthermore, the glutamate signaling cascade in the PFC is suggested to be a potential therapeutic target to prevent the progression of drug addiction.</p>

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