Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice

The function of the central cannabinoid receptor (CB1) was investigated by invalidating its gene. Mutant mice did not respond to cannabinoid drugs, de monstrating the exclusive role of the CB1 receptor in mediating analgesia, reinforcement, hypothermia, hypolocomotion, and hypotension, The acute effe cts of opiates were unaffected, but the reinforcing properties of morphine and the severity of the withdrawal syndrome were strongly reduced. These ob servations suggest that the CB1 receptor is involved in the motivational pr operties of opiates and in the development of physical dependence and exten d the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.