Treatment with AVE0991 attenuated stress-induced increases in corticosterone and glucose, reduced depressive- and anxiety-like behaviors, and prevented BDNF reduction in stressed mice.
RCT
randomly assigned
Does AVE0991 improve behavioral and molecular alterations in mice exposed to chronic unpredictable stress?
The Mas receptor agonist AVE0991 exerts anxiolytic, antidepressant, and neuroprotective effects in a mouse model of chronic unpredictable stress.
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.
Mm et al. (Mon,) conducted a rct in Chronic unpredictable stress. AVE0991 vs. saline was evaluated on stress-induced behavioral and molecular alterations. Treatment with AVE0991 attenuated stress-induced increases in corticosterone and glucose, reduced depressive- and anxiety-like behaviors, and prevented BDNF reduction in stressed mice.