Available online 21 April 2022, 102247

The effects of the peptide ACTH(6–9)-Pro-Gly-Pro at doses of 5; 50; 500 μg/kg on the Wistar rats' behaviour and gut mucosal microbiota composition under conditions of chronic immobilization stress (CRS) were studied. CRS increased anxiety-like and depressive-like behaviour, disturbances in locomotor activity and gut dysbiosis. Administration of ACTH(6–9)-Pro-Gly-Pro showed many phenotypic results. Peptide demonstrated anti-depressant activity at doses of 5 and 500 μg/kg by a decrease in the total immobile time in the FST. ACTH(6–9)-Pro-Gly-Pro administered at a dose of 50 μg/kg resulted in an anxiolytic effect which is shown by an increase in the time in the open arms of EPM (p < 0.05) and a decrease in the time in the closed arms (p < 0.05). Moreover, the peptide led to a decrease in alpha- and beta-diversity of the gut microbiota (p < 0.01). Correlation and linear regression analysis demonstrated central mechanisms of ACTH(6–9)-Pro-Gly-Pro anxiolytic activity and both central and peripheral ones in an anti-depressant effect. In this way, peptide ACTH(6–9)-Pro-Gly-Pro could prevent the development of behavioural disturbances and gut dysbiosis caused by chronic restraint stress.

ACTH(6–9)-Pro-Gly-Pro

Chronic restraint stress

Gut-brain axis

Anxiety-like behaviour

Depressive-like behaviour

Gut microbiota

adrenocorticotropic hormone

central nervous system

chronic restraint stress

hypothalamic-pituitary-adrenal axis

low enzymatic activity

matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectrometry

normal enzymatic activity

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