Interaction between glutamatergic-NMDA and cholinergic-muscarinic systems in classical fear conditioning.
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.
Figueredo
Larissa Zeggio Perez
LZ
Universidade Federal de São Paulo, Departamento de Psicobiologia, São Paulo, SP, Brazil. lzfigueredo@psicobio.epm.br
Moreira
Karin Monteiro
KM
Ferreira
Tatiana Lima
TL
Fornari
Raquel Vecchio
RV
Oliveira
Maria Gabriela Menezes
MG
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004025:Dicyclomine / Q000378:metabolism / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004025:Dicyclomine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate