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 of rats (11). Acute ethanol increased dopamine levels in the nucleus accumbens to a greater extent in KOR−/− mice than in wild-type mice, and nor-binaltorphimine increased ethanol-evoked dopamine levels (12). Chronic ethanol treatment led to increased dynorphin B in the nucleus accumbens which persisted at least 21 days after ceasing treatment (13). The κ-opioid system also appears to be involved in ethanol withdrawal-related seizures (14–16).
