title: Angiotensin-(1-7)/Mas axis modulates fear memory and extinction in mice.
abstract: Inappropriate defense-alerting reaction to fear is a common feature of neuropsychiatric diseases. Therefore, impairments in brain circuits, as well as in molecular pathways underlying the neurovegetative adjustments to fear may play an essential role on developing neuropsychiatric disorders. Here we tested the hypothesis that interfering with angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis homeostasis, which appears to be essential to arterial pressure control, would affect fear memory and extinction. Mas knockout (MasKO) mice, in FVB/N background, showed normal cued fear memory and extinction, but increased freezing in response to context. Next, as FVB/N has poor performance in contextual fear memory, we tested MasKO in mixed 129xC57BL/6 background. MasKO mice behaved similarly to wild-type (WT), but memory extinction was slower in contextual fear conditioning to a weak protocol (1CS/US). In addition, delayed extinction in MasKO mice was even more pronounced after a stronger protocol (3CS/US). We showed previously that Angiotensin II receptor AT1 antagonist, losantan, rescued object recognition memory deficit in MasKO mice. Here, losartan was also effective. Memory extinction was accelerated in MasKO mice after treatment with losartan. In conclusion, we showed for the first time that Ang-(1-7)/Mas axis may modulate fear memory extinction. Furthermore, we suggest MasKO mice as an animal model to study post-traumatic stress disorder (PTSD).
authors.affiliation: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Thiago Luiz do Nascimento
authors.initials: TL
authors.lastname: Lazaroni
authors.affiliation: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Cristiane Perácio
authors.initials: CP
authors.lastname: Bastos
authors.affiliation: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Márcio Flávio Dutra
authors.initials: MF
authors.lastname: Moraes
authors.affiliation: Laboratório de Hipertensão, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Robson Souza
authors.initials: RS
authors.lastname: Santos
authors.affiliation: Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil. Electronic address: grace@icb.ufmg.br.
authors.forename: Grace Schenatto
authors.initials: GS
authors.lastname: Pereira
mesh_terms: D000161:Acoustic Stimulation; D000803:Angiotensin I / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology*; D004597:Electroshock; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D010446:Peptide Fragments / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan
keywords: AT1 receptors; Angiotensin-(1-7)/Mas axis; Fear memory; Fear memory extinction