Pertussis toxin inhibits morphine analgesia and prevents opiate dependence

Six days after intracerebroventricular pretreatment of rats with pertussis toxin (PTX 0.5 microgram/rat) there was a marked decrease in the antinociceptive effect of morphine, regardless of the route of opioid administration (into the periaqueductal gray matter, intrathecally or intraperitoneally) or the analgesic test used (tail flick and jaw opening reflex). PTX pretreatment also partially attenuated the naloxone-precipitated withdrawal syndrome in morphine-dependent rats, significantly reducing teeth chattering, rearing and grooming. These in vivo findings indicate that G-protein-dependent mechanisms are involved in morphine analgesia and dependence. The biochemical mechanism could be related to ADP ribosylation of Gi coupled to the adenylate cyclase system, but an interaction of PTX with other G-proteins linked to different second messengers or directly to ionic channels cannot be excluded.