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Involvement of the dorsal hippocampus muscarinic receptors in the modulation of conditioned emotional response in rats: possible interaction with nitrergic and glutamatergic neurotransmission

Grant number: 13/07419-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2015
Effective date (End): March 31, 2017
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Leonardo Resstel Barbosa Moraes
Grantee:Leandro Antero da Silva
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders, AP.TEM

Abstract

During aversive situations there is an increase in the acetylcholine (ACh) in rat dorsal hippocampus (DH,) especially in animals exposed to contextual fear conditioning (CFC), an animal model important in the study of defensive responses. This increase is related to the activation of muscarinic receptors that would modulate autonomic and behavioral responses observed in this model. This set of responses is usually called "conditioned emotional response" (CER). Microinjection of M1 and M3 muscarinic antagonist in the HD rats, attenuate these responses, suggesting a modulatory role of cholinergic neurotransmission about the CER. However, there are other systems involved in this modulation, can interact with the cholinergic system. Similarly, administration of inhibitors of the production of nitric oxide (NO) and NMDA receptor antagonists in the DH rat also decreased the CER during the reexposure context. Thus, this study investigates the interaction between these systems in the modulation of contextual CER. Thus, we will investigate whether the ACh increase in the DH rat conditioned by administration of an acetylcholinesterase inhibitor, before re-exposure to aversive context, could increase the CER, with consequent production of NO. Thereafter, we will evaluate the involvement of M1 and M3 receptors in the modulation these responses, with prior administration of their respective selective antagonists. The involvement of glutamatergic and nitrergic systems in the modulation of CER generated by increased ACh in the HD, will also be assessed. Thus, we will administer NO-GCs pathway inhibitors or NMDA receptor antagonists. The cultures of hippocampal cells are important in the more accurate quantification of the levels of NO and nNOS activity after previous stimulation of ACh. The participation of M1 and M3 muscarinic receptors in the generation of these responses will be assessed. (AU)

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