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Title: Antidepressant-like effect of terpineol in an inflammatory model of depression : involvement of the cannabinoid system and d2 dopamine receptor.
Authors: Vieira, Graziela
Cavalli, Juliana
Gonçalves, Elaine Cristina Dalazen
Braga, Saulo Fehelberg Pinto
Ferreira, Rafaela Salgado
Santos, Adair Roberto Soares
Cola, Maíra
Raposo, Nádia Rezende Barbosa
Capasso, Raffaele
Dutra, Rafael Cypriano
Keywords: Terpenoids
Dopaminergic receptor
Issue Date: 2020
Citation: VIEIRA, G. et al. Antidepressant-like effect of terpineol in an inflammatory model of depression: involvement of the cannabinoid system and d2 dopamine receptor. Biomolecules, v. 10, 2020. Disponível em: <>. Acesso em: 11 out. 2022.
Abstract: Depression has a multifactorial etiology that arises from environmental, psychological, genetic, and biological factors. Environmental stress and genetic factors acting through immunological and endocrine responses generate structural and functional changes in the brain, inducing neurogenesis and neurotransmission dysfunction. Terpineol, monoterpenoid alcohol, has shown immunomodulatory and neuroprotective effects, but there is no report about its antidepressant potential. Herein, we used a single lipopolysaccharide (LPS) injection to induce a depressive-like effect in the tail suspension test (TST) and the splash test (ST) for a preventive and therapeutic experimental schedule. Furthermore, we investigated the antidepressant-likemechanism of action of terpineol while usingmolecular and pharmacological approaches. Terpineol showed a coherent predicted binding mode mainly against CB1 and CB2 receptors and also against the D2 receptor during docking modeling analyses. The acute administration of terpineol produced the antidepressant-like effect, since it significantly reduced the immobility time in TST (100–200 mg/kg, p.o.) as compared to the control group. Moreover, terpineol showed an antidepressant-like effect in the preventive treatment that was blocked by a nonselective dopaminergic receptor antagonist (haloperidol), a selective dopamine D2 receptor antagonist (sulpiride), a selective CB1 cannabinoid receptor antagonist/inverse agonist (AM281), and a potent and selective CB2 cannabinoid receptor inverse agonist (AM630), but it was not blocked by a nonselective adenosine receptor antagonist (caffeine) or a β-adrenoceptor antagonist (propranolol). In summary, molecular docking suggests that CB1 and CB2 receptors are the most promising targets of terpineol action. Our data showed terpineol antidepressant-like modulation by CB1 and CB2 cannabinoid receptors and D2-dopaminergic receptors to further corroborate our molecular evidence.
ISSN: 2218-273X
metadata.dc.rights.license: This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( Fonte: o PDF do artigo.
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