Differential prevention of morphine amnesia by antisense oligodeoxynucleotides directed against Gi-protein a subunits.

1 The e ect of the i.c.v. administration of pertussis toxin (PTX) and antisense oligodeoxynucleotide directed against the a subunit of di erent Gi-proteins (anti-Gia1, anti-Gia2, anti-Gia3) on amnesia induced by morphine was evaluated in the mouse passive avoidance test. 2 The administration of morphine (6 ± 10 mg kg71 i.p.) immediately after the training session produced amnesia that was prevented by PTX (0.25 mg per mouse i.c.v.) administered 7 days before the passive avoidance test. 3 Anti-Gia1 (6.25 mg per mouse i.c.v.) and anti-Gia3 (12.5 mg per mouse i.c.v.), administered 18 and 24 h before the training session, prevented the morphine amnesia. By contrast, pretreatment with anti-Gia2 (3.12 ± 25 mg per mouse i.c.v.) never modi®ed the impairment of memory processes induced by morphine. 4 At the highest e ective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modi®ed spontaneous motility and inspection activity, as revealed by the hole board test. 5 These results suggest the important role played by Gi1 and Gi3 protein subtypes in the transduction mechanism involved in the impairment of memory processes produced by morphine.