Targeting 2-arachidonoylglycerol signalling in the neurobiology and treatment of depression.
Basic Clin Pharmacol Toxicol
; 129(1): 3-14, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-33905617
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Psicológico
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Transdução de Sinais
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Ácidos Araquidônicos
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Endocanabinoides
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Transtorno Depressivo Maior
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Glicerídeos
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Antidepressivos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Basic Clin Pharmacol Toxicol
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Reino Unido