Interaction between glutamatergic-NMDA and cholinergic-muscarinic systems in classical fear conditioning

Abstract

A number of studies have suggested that the glutamatergic and cholinergic systems are both involved in learning and memory processes and that they interact in order to facilitate these processes. However, the role of M1-muscarinic receptors in mediating this interaction has not been elucidated. The aim of this study was to determine whether the concomitant administration of MK-801 (non-competitive NMDA antagonist) and dicyclomine (M1-muscarinic antagonist--DIC) in sub-effective doses impairs contextual fear conditioning (hippocampal-dependent task) and tone fear conditioning tasks (hippocampal-independent task). The results showed that concomitant pre-training administration of DIC (8.0 mg/kg) and MK-801 (0.07 mg/kg)--two sub-effectives doses for the contextual fear conditioning task--does impair the performance of animals on this task (as measured by freezing behavior time). Tone fear conditioning tasks were not affected by the drugs either administered separately or concurrently. The pre-training administration of sub-effective doses of MK-801 and DIC in combination impairs performance on contextual fear conditioning task (hippocampal-dependent), but not on tone fear conditioning task (hippocampal-independent). These data support the hypothesis that the interaction between glutamatergic and cholinergic systems in hippocampus-dependent learning and memory processes probably occurs through M1 receptor.