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| Item Type: | Article |
|---|---|
| Title: | The nonpeptide angiotensin-(1-7) mimic AVE0991 attenuates neuroendocrine and behavioral responses to chronic unpredictable stress |
| Creators: |
Fonseca, Maria Luiza Antunes, de Oliveira Amaral, Laura Beatriz, Gonçalves, Sthéfanie C.A., Costa, Laura A., de Oliveira, Laura Barroso Ferreira, Mourão, Flávio A.G., Fontes, Marco Antônio Peliky, Bader, Michael  ORCID: https://orcid.org/0000-0003-4780-4164, Santos, Robson A.S., Campagnole-Santos, Maria José and Kangussu, Lucas M. ORCID: https://orcid.org/0000-0003-3678-118X
|
| Abstract: | RATIONALE: Chronic stress, frequently associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and reduced neuroplasticity, is a major risk factor for psychiatric disorders such as anxiety and depression. OBJECTIVE: The present study aimed to validate a 21-day chronic unpredictable stress (CUS) model and to investigate the effects of the Mas receptor agonist AVE0991 on stress-induced behavioral and molecular alterations. METHODS: Male C57BL/6J mice were exposed to a 21-day CUS protocol. Animals were randomly assigned to four groups: control + saline, CUS + saline, control + AVE0991, and CUS + AVE0991 (3 mg/kg, i.p.). AVE was administered daily during the last two weeks of the stress protocol. Behavioral tests were performed to evaluate anxiety- and depressive-like behaviors, and plasma corticosterone, blood glucose levels, and brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex, hippocampus, and hypothalamus were measured. RESULTS: CUS exposure significantly increased plasma corticosterone and glucose levels and induced anxiety- and depressive-like behaviors. Stressed animals also showed reduced BDNF levels in the prefrontal cortex, hippocampus, and hypothalamus. Treatment with AVE0991 attenuated the increase in corticosterone and prevented stress-induced hyperglycemia. Moreover, AVE0991 reduced depressive-like behavior, increased latency to immobility, and improved anxiety-related parameters in the elevated plus maze and open field tests without affecting locomotor activity. AVE0991 also prevented the reduction of BDNF levels in stress-exposed animals. CONCLUSION: These findings validate the CUS model and demonstrate that activation of the Mas receptor by AVE0991 exerts anxiolytic, antidepressant, and neuroprotective effects, supporting its potential as a therapeutic strategy for stress-related neuropsychiatric disorders. |
| Keywords: | Chronic Unpredictable Stress, Anxiety, Depression, AVE0991, BDNF |
| Source: | Psychopharmacology |
| ISSN: | 0033-3158 |
| Publisher: | Springer |
| Date: | 13 July 2026 |
| Official Publication: | https://doi.org/10.1007/s00213-026-07126-4 |
| PubMed: | View item in PubMed |
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