Enkephalin, antinociceptive action

The availability of receptor knockout animals has also helped to illustrate cannabinoid-opioid interactions. CBi receptor knockout mice had greatly reduced morphine self-administration behavior and less severe naloxone-induced withdrawal signs than wild type animals, although the antinociceptive actions of morphine were unaffected in the knockout animals (40). The rimona-bant-precipitated withdrawal syndrome in THC-treated mice was significantly attenuated in animals with knockout of the pro-enkephalin gene (48). Knockout of the p opioid (OP3) receptor also reduced rimonabant-induced withdrawal signs in THC-treated mice, and there was an attenuated naloxone withdrawal syndrome in morphine-dependent CBi knockout mice (49,50). 

Recently, the endogenous morphine receptor ligand, enkephalin, has been iso= lated [305], identified chemically [306], and found to possess antinociceptive activity in mice after ICV injection [307], The interactions of the amines, enkephalin, and the cyclic nucleotides remain to be determined, and the scope for future studies of the mechanisms of action of the opiate analgesics becomes much wider as a result of these more recent studies. 

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