Absence of Delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice

The involvement of dynorphin on Delta -9-tetrahydrocannabinol (THC) and mor phine responses has been investigated by using mice with a targeted inactiv ation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specif ic changes in the behavioral effects of THC, including a reduction of spina l THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of nega tive motivational effects of THC in the absence of dynorphin demonstrates t hat this endogenous opioid peptide mediates the dysphoric effects of mariju ana.