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 a nd 0.50 mu g per mouse i.c.v. on the analgesic effect produced by morp hine (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 physostigmin e (0.1-0.2 mg kg(-1) s.c.) was investigated in the mouse hot-plate tes t. Seven days after a single injection of pertussis toxin, inhibition of morphine and diphenhydramine analgesia was observed, whereas 11 day s after pertussis toxin pretreatment, baclofen- and clomipramine-induc ed antinociception was also reduced. By contrast, pertussis toxin had no effect on physostigmine-induced antinociception. The present result s indicate that the activation of pertussis toxin-sensitive G-proteins represents an important transduction step in the central analgesia in duced by opioids, antihistaminics, GABA(B) (gamma-aminobutyric acid B) agonists acid tricyclic antidepressants, but not by cholinomimetics.