The dynorphin (DYN)/kappa-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacologic manipulations.
Increased DYN A and increased KOR signaling could set the stage for a one-two punch during withdrawal that drives excessive alcohol consumption in alcohol dependence. Importantly, intracentral nucleus of the amygdala pharmacologic challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive alcohol consumption during withdrawal.
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