Galanin is a neuropeptide with appetitive, antinociceptive and neuroendocrine functions. Galanin and galanin binding sites are present in brain areas that mediate reinforcement, such as nucleus accumbens and ventral tegmental area, as well as locus coeruleus, an area known to be involved in development of drug dependence and withdrawal. This localization, coupled with the observation that there is a strong interaction between morphine and galanin in spinal cord, made it of interest to study whether galanin might have effects on morphine reinforcement. Using the place preference paradigm we found that galanin (1 microg i.c.v.) alone does not possess reinforcing or aversive properties but attenuates the preference conditioned by peripheral administration of morphine (5 mg/kg s.c.). Quantitative receptor autoradiography showed that morphine treatment that could condition a place preference decreased galanin binding in the nucleus accumbens and increased galanin binding in the locus coeruleus. In contrast, acute naltrexone administration increased galanin binding in the nucleus accumbens, suggesting that levels of galanin binding are tonically regulated by opioid receptors in that area. Contrary to what is seen in the spinal cord, these results indicate that galanin and morphine have an antagonistic interaction in the brain that results in attenuation of morphine reinforcement by activation of the galaninergic system.