Intranasal administration of transforming growth factor-β1 elicits rapid-acting antidepressant-like effects in a chronic social defeat stress model: A role of TrkB signaling.

Intranasal administration of transforming growth factor-β1 elicits rapid-acting antidepressant-like effects in a chronic social defeat stress model: A role of TrkB signaling.

Publication date: Sep 01, 2021

(R,S)-ketamine causes rapid-acting and sustained antidepressant effects in treatment-resistant patients with depression although the precise molecular mechanisms underlying its antidepressant action remain unclear. We recently reported that transforming growth factor (TGF)-β1 might contribute to the antidepressant-like effects of (R)-ketamine that is a more potent enantiomer in rodents. Although TrkB signaling plays a role in the antidepressant-like actions of (R,S)-ketamine and its enantiomers, the role of TrkB signaling in the antidepressant effects of TGF-β1 remains unclear. Using behavioral tests such as tail-suspension test (TST), forced swimming test (FST), and 1% sucrose preference test (SPT), we investigated whether a single intranasal administration of the recombinant TGF-β1 (1. 5 and 3. 0 μg/kg) causes rapid and sustained antidepressant-like effects in a chronic social defeat stress (CSDS) model. Both doses of TGF-β1 significantly attenuated the increased immobility time of TST and FST in the CSDS susceptible mice. High dose of TGF-β1, but not low dose, significantly ameliorated the decreased sucrose preference of SPT in the CSDS susceptible mice. Pretreatment with a TrkB antagonist ANA-12 (0. 5 mg/kg) blocked the antidepressant-like effects of TGF-β1 in CSDS susceptible mice. The data suggest that intranasal administration of TGF-β1 could elicit rapid-acting antidepressant-like effects via TrkB stimulation in a CSDS model. Therefore, it is likely that intranasal administration of TGF-β1 would be a novel therapeutic approach for depression.

Concepts Keywords
Antidepressant Psychoactive drugs
Increased Branches of biology
Neuropsychopharmacol Antidepressants
Rodents Ketamine
Swimming Tail suspension test
Nasal administration
ANA-12
Brain-derived neurotrophic factor

Semantics

Type Source Name
disease MESH growth
drug DRUGBANK Ketamine
disease MESH depression
drug DRUGBANK Sucrose

Original Article

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