Evidence for a possible functional interaction between serotonergic and cholinergic mechanisms in memory retrieval.

A total of three experiments were conducted. In Experiment 1, the dose-dependent effects of the pretest administration of the serotonergic agonist alaproclate and the selective muscarinic cholinergic agonist oxotremorine, alone and in combination, were assessed in a one-trial inhibitory avoidance task. A clear dose-dependent enhancement of performance was demonstrated as a result of all three treatment conditions, which could not be explained in terms of nonspecific effects of the drugs on behavior in general. In addition, the facilitation of retrieval performance produced by the combined treatment of alaproclate and oxotremorine was observed at dose levels well below those observed following administration of either compound alone. In Experiment 2 attempts were made to block the enhancements of retention resulting from the different treatment conditions (alaproclate, oxotremorine, or the combination of alaproclate and oxotremorine) by pretreating the mice with either scopolamine (a muscarinic cholinergic antagonist) or quipazine (a serotonergic agonist). The results of these experiments indicate that (a) quipazine completely blocked the enhancement of retrieval resulting from alaproclate but not that following oxotremorine or oxotremorine in combination with alaproclate, while (b) scopolamine blocked the enhancement of retrieval resulting from oxotremorine alone as well as that resulting from alaproclate plus oxotremorine but failed to block the memory enhancement resulting from alaproclate. The present results lend further support to the view that both serotonin and acetylcholine play important roles in memory retrieval. More importantly, the results of the present series of experiments provide additional support for a functional interaction between the serotonergic and cholinergic nervous systems in the mediation of behavior.