GABA in morphine analgesia and tolerance

Drugs affecting various steps of GABA transmission exhibit analgesia in a variety of experimental models in animals; this analgesic response generally requires high doses of the drugs and does not appear to be opiate-like since the GABAergic analgesia is naloxone-insensitive and lacks dependence liability. The outcome of the analgesia response is variable when opiate and GABAergic drugs are administered together; however, directly acting GABA receptor stimulants and GABA-transaminase inhibitors generally enhance the analgesic effect of opiates. The development of newer GABAergic drugs with greater potency and specificity may offer an alternative to opiate analgesics. The results obtained over the years, on the possible involvement of the GABA system in morphine tolerance and dependence are equivocal. Studies on region-specific changes in opiate-GABA interaction as well as opiate-GABA-benzodiazepine interaction are needed to further elucidate the role of GABA on opiate system.