Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN.

Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN. Neuropharmacology. 2018 Mar 14;135:163-171 Authors: Diniz CRAF, Casarotto PC, Fred SM, Biojone C, Castrén E, Joca SRL Abstract The renin-angiotensin system (RAS) is associated with peripheral fluid homeostasis and cardiovascular function, but recent evidence also suggests a functional role in the brain. RAS regulates physiological and behavioral parameters related to the stress response, including depressive symptoms. Apparently, RAS can modulate levels of brain-derived neurotrophic factor (BDNF) and TRKB, which are important in the neurobiology of depression and antidepressant action. However, the interaction between the BDNF/TRKB system and RAS in depression has not been investigated before. Accordingly, in the forced swimming test, we observed an antidepressant-like effect of systemic losartan but not with captopril or enalapril treatment. Moreover, infusion of losartan into the ventral hippocampus (vHC) and prelimbic prefrontal cortex (PL) mimicked the consequences of systemically injected losartan, whereas K252a (a blocker of TRK) infused into these brain areas impaired such effect. PD123319, an antagonist of AT2 receptor (AGTR2), also prevented the systemic losartan effect when infused into PL but not into vHC. Cultured cortical cells of rat embryos revealed that angiotensin II (ANG2), possibly ...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research