The combination of ethanol and cocaine is commonly abused by human addicts which has serious clinical consequences. Here, the effects of separately and concurrently administered ethanol and 'binge' cocaine on kappa opioid receptor (KOR) mRNA in the ventral tegmental area (VTA) and nucleus accumbens (NAc) of rats were studied. KOR mRNA was down-regulated in both brain regions during concurrent as well as separate treatment with these drugs. In the VTA, the most pronounced decrease was obtained following combined treatment with ethanol and 'binge' cocaine. In the NAc, the strongest decrease was observed in the 'binge' cocaine group. This profound decrease of KOR mRNA in regions important for brain reward suggests a potential role of the KOR system in the abuse of cocaine and ethanol.