Opioids regulate many brain functions relevant to addictions, including reward, reinforcement, mood and psychomotor stimulation (1–5). In particular, stimulation of the κ-opioid receptor (KOR) reduces the release of dopamine in the nucleus accumbens of the mouse and generates aversive states (1,2). The effects of stimulating or inhibiting the κ-opioid system are complex and may be affected by species, strain, duration of exposure and drinking paradigm (6). Stimulating the KOR with a selective KOR agonist reduces voluntary ethanol intake in rats in a two-bottle choice paradigm (7), but chronic treatment potentiated ethanol intake during the alcohol deprivation effect in rats that had long-term exposure to ethanol (3). Blocking the KOR in mice that normally drink ethanol (C57/BL6) with a KOR-specific antagonist, nor-binaltorphimine, increases alcohol self-administration (8). Walker and Koob (9) reported that nor-binaltorphimine selectively reduced ethanol self-administration in rats made dependent on ethanol but not in non-dependent rats. Mice in which the KOR has been disrupted drink half as much ethanol as either wild-type or heterozygous mice (10). Ethanol treatment, particularly in combination with cocaine, reduces KOR mRNA in the VTA
