μ-Opioid receptors in the nucleus accumbens shell mediate context-induced reinstatement (renewal) but not primed reinstatement of extinguished alcohol seeking.

Opioid antagonists reduce the rate of relapse to drinking in clinical trials and reduce reinstatement in animal models of drug seeking. However, the neuroanatomical locus for this effect remains poorly understood. We examined the role of nucleus accumbens shell (AcbSh) μ-opioid receptors in two different forms of recovery of alcoholic beer seeking. Rats were trained to nosepoke for alcoholic beer in a distinctive context and this response was then extinguished. Response recovery was produced via renewal (context-induced reinstatement) (Experiment 1) or primed reinstatement (Experiment 2). Rats received microinjections of the μ-opioid receptor antagonist CTAP before these tests. AcbSh microinfusion of 2.5 μg CTAP attenuated the ABA renewal of alcoholic beer seeking in a neuroanatomically specific manner. In contrast, AcbSh microinfusion of 2.5 μg or 5 μg CTAP had no effect on the primed reinstatement of alcoholic beer seeking. These findings indicate a role for AcbSh μ-opioid receptors in renewal of alcoholic beer seeking and suggest that there are dissociable ventral striatal substrates for different forms of recovery of extinguished alcoholic beer seeking.