Effects of oxotremorine on inhibitory avoidance behaviour in two inbred strains of mice: interaction with 5-methoxy-NN-dimethyltriptamine.

In mice, the drug oxotremorine, which stimulates the cholinergic system, improved memory retention in a dose-dependent way, while 5-MeODMT, a serotonergic agonist, impaired it. DBA/2 mice were more sensitive to oxotremorine than C57BL/6 mice, but strain differences did not affect response to the serotonergic drug. When both drugs were given together, the memory improvement from oxotremorine was blocked. The findings confirm that cholinergic activity aids memory and suggest that serotonergic activity inhibits memory, with an interaction between the two systems during memory consolidation.

Study at a glance

Abstract

The effects of the cholinergic muscarinic agonist, oxotremorine (0.005, 0.01, 0.02 and 0.04 mg/kg), the serotonergic agonist, 5-methoxy-NN-dimethyltriptamine (5-MeODMT) (0.5, 1 and 2 mg/kg), and their combination, were investigated in C57BL/6 and DBA/2 mice using a one-trial inhibitory avoidance task, drug treatment being given immediately after the acquisition trial. Post-trial administration of oxotremorine facilitated, while post-trial administration of 5-MeODMT inhibited memory retention of both strains in a dose-dependent fashion. The DBA/2 strain was more affected by oxotremorine than the C57BL/6 mice; no strain-dependent sensitivity to serotonergic agonist administration was observed. In both strains, the combination of oxotremorine plus 5-MeODMT inhibited the performance improvement shown by the administration of the cholinergic agonist alone. The facilitatory role of cholinergic stimulation on retention performance was confirmed and an inhibitory action of the serotonergic system on memory processes was suggested. Moreover, the present results support a functional interaction between cholinergic and serotonergic systems on memory consolidation.