Morphine self-administration in mu-opioid receptor-deficient mice

Morphine-induced place preference was demonstrated recently in wild-type mi ce, whereas this conditioned behaviour was not observed in mu-opioid recept or-deficient mice. In the present study, we investigated locomotor effects of subcutaneously (s.c.) injected morphine as well as intracerebroventricul ar (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mic e. After s.c. morphine injection, locomotor activity significantly increased i n wild-type animals. As expected. in the self-administration test the rate of self-administration constantly increased in wild-type mice reflecting re ward effects of morphine. This increase was independent of locomotor/motor activity. In contrast, self-administration rates and locomotor/motor activi ty significantly decreased in the receptor-deficient animals. It was shown that this aversive effect might partly be due to kappa-opioid receptor inte raction.