Differential involvement of hippocampal G-protein subtypes in the memory process of rats.

Inactivation of Gi and G(o) proteins in the dentate gyrus of the hippocampus by pertussis toxin did not affect memory retention of a one-way passive avoidance learning task in rats. Interference of normal Gs activity in the dentate gyrus by cholera toxin impaired retention performance dose-dependently. Cholera toxin also antagonized the memory-enhancing effect of corticotropin-releasing factor in the hippocampus. However, although Gi and G(o) proteins are probably not involved in the memory consolidation process per se, in animals showing a full retention score there was a significant and long-lasting increase of G(o) concentration in the dentate gyrus. Results of ADP-ribosylation experiments have shown that there was a dose-dependent decrease of ADP-ribosylation in vitro as the concentration of in vivo pertussis toxin and cholera toxin increased. These results together suggest that Gs protein is probably involved in the initiation of the memory consolidation process, while enhanced G(o) expression is the ultimate result upon memory formation. These results provide the first in vivo evidence relating the functions of hippocampal G proteins to the memory process of mammals.