Differential prevention of morphine amnesia by antisense oligodeoxynucleotides directed against various Gi-protein alpha subunits

1 The effect of the i.c.v. administration of pertussis toxin (PTX) and anti sense oligodeoxynucleotide directed against the cc subunit of different Gi- proteins (anti-Gi(alpha1), anti-Gi(alpha2), anti-Gi(alpha3)) on amnesia ind uced by morphine was evaluated in the mouse passive avoidance test. 2 The administration of morphine (6-10 mg kg(-1) i.p.) immediately after th e training session produced amnesia that was prevented by PTX (0.25 mug per mouse i.c.v.) administered 7 days before the passive avoidance test. 3 Anti-Gi(alpha1) (6.25 mug per mouse i.c.v.) and anti-Gi(alpha3) (12.5 mug per mouse i.c.v.), administered 18 and 24 h before the training session, p revented the morphine amnesia. By contrast, pretreatment with anti-Gi(alpha 2) (3.12-25 mug per mouse i.c.v.) never modified the impairment of memory p rocesses induced by morphine. 4 At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous m otility and inspection activity, as revealed by the hole board test. 5 These results suggest the important role played by Gi(1) and Gi(3) protei n subtypes in the transduction mechanism involved in the impairment of memo ry processes produced by morphine.