Effect of pertussis toxin on morphine, diphenhydramine, baclofen, clomipramine and physostigmine antinociception.

The effect of pretreatment with pertussis toxin at the doses of 0.25 and 0.50 micrograms per mouse i.c.v. on the analgesic effect produced by morphine (7 mg kg-1 s.c.), baclofen (4 mg kg-1 s.c.), diphenhydramine (20 mg kg-1 s.c.), clomipramine (25 mg kg-1 s.c.) and physostigmine (0.1-0.2 mg kg-1 s.c.) was investigated in the mouse hot-plate test. Seven days after a single injection of pertussis toxin, inhibition of morphine and diphenhydramine analgesia was observed, whereas 11 days after pertussis toxin pretreatment, baclofen- and clomipramine-induced antinociception was also reduced. By contrast, pertussis toxin had no effect on physostigmine-induced antinociception. The present results indicate that the activation of pertussis toxin-sensitive G-proteins represents an important transduction step in the central analgesia induced by opioids, antihistaminics, GABAB (gamma-aminobutyric acid B) agonists and tricyclic antidepressants, but not by cholinomimetics.