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

Abstract

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-Gia 1 , anti-Gia 2 , anti-Gia 3 ) on amnesia induced by morphine was evaluated in the mouse passive avoidance test. 2 The administration of morphine (6 ± 10 mg kg 71 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-Gia 1 (6.25 mg per mouse i.c.v.) and anti-Gia 3 (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-Gia 2 (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 Gi 1 and Gi 3 protein subtypes in the transduction mechanism involved in the impairment of memory processes produced by morphine.

Intradorsal hippocampal microinjection of lithium reverses morphine-induced impairment of memory in mice: interactions with dopamine receptor mechanism(s)

“…The activation of these receptors, which inhibit adenylyl cyclase through Gi/o types of G-proteins (Law et al, 1999(Law et al, , 2000, is required for morphine to induce amnesia in the mouse passive avoidance test (Galeotti et al, 2001). Interestingly, the present results showed that intra-CA1 administration of different doses of lithium on the test day also reversed the decrease in the step-down latency induced by posttraining morphine.…”

10.1007/s10525-008-1007-y

“…Numerous experiments demonstrated negative effects of morphine, enkephalins, and their derivatives on active and passive avoidance conditioning (Martinez, 1992;Galeotti et al, 2001). Similar data were obtained during learning with oxidative reinforcement-both during the development of operative responses and in maze tests (Vlasova et al, 1983;Pakarinen et al, 1995).…”