Addiction is associated with a high risk of relapse long after physical signs of withdrawal have ceased. Relapse can occur after years of abstinence. Cues previously associated with a drug may trigger relapse even after a lengthy period of abstinence. In rat models of drug self-administration followed by prolonged withdrawal (30 days), the presentation of cues previously associated with cocaine47 or alcohol48 can increase levels of p-ERK in the amygdala. Administration of an NMDA receptor antagonist decreases p-ERK and drug-seeking behavior, suggesting that p-ERK facilitates cocaine seeking through an NMDA-dependent mechanism.47,49
