The endocannabinoid system and NGF are involved in the mechanism of action of resveratrol: a multi-target nutraceutical with therapeutic potential in neuropsychiatric disorders

• Published in: Psychopharmacology 2016-03, Vol.233 (6), p.1087-1096
• Main Authors: Hassanzadeh, Parichehr, Arbabi, Elham, Atyabi, Fatemeh, Dinarvand, Rassoul
• Format: Article
• Language: English
• Subjects: Amitriptyline - pharmacology; Animals; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Bornanes - pharmacology; Brain - drug effects; Brain - metabolism; Cannabinoids; Cannabinoids - pharmacology; Clonazepam - pharmacology; Dose-Response Relationship, Drug; Endocannabinoids - metabolism; Growth factors; Health aspects; Male; Nerve Growth Factor - metabolism; Neurobiology; Neuropsychology; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Piperidines - pharmacology; Polyphenols; Psychiatry; Psychopharmacology; Psychotic disorders; Pyrazoles - pharmacology; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB2; Resveratrol; Signal Transduction - drug effects; Stilbenes - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-015-4188-3

Rationale Resveratrol is a polyphenolic compound with antioxidant, anti-inflammatory, and neuroprotective effects. It has also shown antidepressant-like effects in the behavioral studies; however, its mechanism(s) of action merit further evaluation. Objectives The interaction between the nerve growth factor (NGF) and endocannabinoid system (eCBs) and their contribution to the antidepressant or emotional activity prompted us to evaluate their implications in the mechanism of action of resveratrol. Methods After single and 4-week intraperitoneal (i.p.) once-daily injections of resveratrol (40, 80, and 100 mg/kg), amitriptyline (2.5, 5, and 10 mg/kg), or clonazepam (10, 20, and 40 mg/kg) into male Wistar rats, eCB and NGF contents were quantified in the brain regions implicated in the modulation of emotions by isotope-dilution liquid chromatography/mass spectrometry and Bio-Rad protein assay, respectively. In the case of any significant alteration of brain eCB or NGF level, the effect of pre-treatment with cannabinoid CB 1 or CB 2 receptor antagonist (AM251 or SR144528) was investigated. Results Four-week treatment with resveratrol or amitriptyline resulted in a significant and sustained enhancement of NGF and eCB contents in dose-dependent and brain region-specific manner. Neither acute nor 4-week treatment with clonazepam affected brain eCB or NGF contents. Pre-treatment with AM251 (3 mg/kg), but not SR144528, prevented the enhancement of NGF protein levels. AM251 exhibited no effect by itself. Conclusions Resveratrol like the classical antidepressant, amitriptyline, affects brain NGF and eCB signaling under the regulatory drive of CB 1 receptors.