Extinction of ethanol-seeking behavior: the role of extracellular signal-regulated kinase signaling and medial prefrontal cortex circuitry in extinction of ethanol-induced conditioned place preference in mice

Extinction of ethanol-induced conditioned place preference (EtOH-CPP) remains poorly understood compared to acquisition and expression phases. This study systematically examined the neurochemistry and neurocircuitry underlying EtOH-CPP extinction in mice. Manipulations of ERK signaling using D-cycloserine (DCS) or SL327 did not impair extinction, suggesting ERK pathways are not critical for this process. In contrast, immunohistochemistry and electrolytic lesion experiments indicated that the medial prefrontal cortex (mPFC) is essential for extinction. Attempts to employ extinction-specific intra-mPFC microinjections were inconclusive due to incomplete extinction in controls. These findings provide the first comprehensive evidence implicating mPFC involvement in EtOH-CPP extinction, while ERK signaling appears non-essential.