Combined treatment with galanthaminium bromide, a new cholinesterase inhibitor, and RS 67333, a partial agonist of 5-HT4 receptors, enhances place and object recognition in young adult and old rats.

The present study was designed to investigate whether a combination of a new acetylcholinesterase inhibitor we have synthesized, galanthaminium bromide, and an agonist of 5-hydroxytryptamine(4) receptors, RS 67333, at doses ineffective alone, improves performance in tasks involving place and object recognition memory. Dose responses of each compound were determined in order to select doses without effect alone. Accordingly, young adult rats were injected intraperitoneally with galanthaminium bromide (0.3 mg/kg)+RS 67333 (0.01 mg/kg), and old rats with galanthaminium bromide (0.1 mg/kg for place and 0.3 mg/kg for object recognition)+RS 67333 (1 mg/kg). Drugs were injected before the acquisition phase, immediately after it, or before the retrieval phase to determine the stage of information processing affected by treatments. Doses of galanthaminium bromide and RS 67333, without effect on their own, jointly improved both place and object recognition in young adult rats via an enhancement of acquisition and consolidation information processing. In old rats, the combined treatment enhanced performance by acting on the acquisition processes of place recognition and on the acquisition and consolidation processes of object recognition. These results indicate that combining agents that act on different neuronal targets may be more powerful than either treatment alone, enabling use of lower doses of each compound, thereby attenuating the adverse effects of the individual drugs. A bitherapeutic strategy of this kind might thus be of interest in the treatment of the cognitive deficits related to "normal" or pathological aging.