Differential prevention of morphine amnesia by antisense oligodeoxynucleotides directed against various Gi‐protein α subunits

The effect of the i.c.v. administration of pertussis toxin (PTX) and antisense oligodeoxynucleotide directed against the α subunit of different Gi‐proteins (anti‐Giα 1 , anti‐Giα 2 , anti‐Giα 3 ) on amnesia induced by morphine was evaluated in the mouse passive avoidance test. The administration of morphine (6 – 10 mg kg −1 i.p.) immediately after the training session produced amnesia that was prevented by PTX (0.25 μg per mouse i.c.v.) administered 7 days before the passive avoidance test. Anti‐Giα 1 (6.25 μg per mouse i.c.v.) and anti‐Giα 3 (12.5 μg per mouse i.c.v.), administered 18 and 24 h before the training session, prevented the morphine amnesia. By contrast, pretreatment with anti‐Giα 2 (3.12 – 25 μg per mouse i.c.v.) never modified the impairment of memory processes induced by morphine. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole board test. These results suggest the important role played by Gi 1 and Gi 3 protein subtypes in the transduction mechanism involved in the impairment of memory processes produced by morphine.British Journal of Pharmacology (2001) 133 , 267–274; doi: 10.1038/sj.bjp.0704081