Targeting 2-arachidonoylglycerol signalling in the neurobiology and treatment of depression.

Autor: Silveira KM; School of Pharmaceutical Sciences of Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Ribeirao Preto, Brazil.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Wegener G; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Joca SRL; School of Pharmaceutical Sciences of Ribeirao Preto (FCFRP), University of Sao Paulo (USP), Ribeirao Preto, Brazil.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: Basic & clinical pharmacology & toxicology [Basic Clin Pharmacol Toxicol] 2021 Jul; Vol. 129 (1), pp. 3-14. Date of Electronic Publication: 2021 May 17.
DOI: 10.1111/bcpt.13595
Abstrakt: The endocannabinoid 2-arachidonoylglycerol (2-AG) is an atypical neurotransmitter synthesized on demand in response to a wide range of stimuli, including exposure to stress. Through the activation of cannabinoid receptors, 2-AG can interfere with excitatory and inhibitory neurotransmission in different brain regions and modulate behavioural, endocrine and emotional components of the stress response. Exposure to chronic or intense unpredictable stress predisposes to maladaptive behaviour and is one of the main risk factors involved in developing mood disorders, such as major depressive disorder (MDD). In this review, we describe the molecular mechanisms involved in 2-AG signalling in the brain of healthy and stressed animals and discuss how such mechanisms could modulate stress adaptation and susceptibility to depression. Furthermore, we review preclinical evidence indicating that the pharmacological modulation of 2-AG signalling stands as a potential new therapeutic target in treating MDD. Particular emphasis is given to the pharmacological augmentation of 2-AG levels by monoacylglycerol lipase (MAGL) inhibitors and the modulation of CB2 receptors.
(© 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)
Databáze: MEDLINE
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