Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor.
Animals
Anti-Inflammatory Agents
/ therapeutic use
Antidepressive Agents
/ therapeutic use
Binding Sites
Cannabinoid Receptor Modulators
/ therapeutic use
Depression
/ drug therapy
Dopamine Agents
/ therapeutic use
Hindlimb Suspension
/ adverse effects
Lipopolysaccharides
/ toxicity
Male
Mice
Molecular Docking Simulation
Monoterpenes
/ therapeutic use
Protein Binding
Receptors, Cannabinoid
/ chemistry
Receptors, Dopamine D2
/ chemistry
cannabinoid receptor
depression
dopaminergic receptor
phytocannabinoid
terpenoids
Journal
Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414
Informations de publication
Date de publication:
20 05 2020
20 05 2020
Historique:
received:
21
04
2020
revised:
13
05
2020
accepted:
15
05
2020
entrez:
24
5
2020
pubmed:
24
5
2020
medline:
7
4
2021
Statut:
epublish
Résumé
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-like mechanism of action of terpineol while using molecular 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.
Identifiants
pubmed: 32443870
pii: biom10050792
doi: 10.3390/biom10050792
pmc: PMC7280984
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antidepressive Agents
0
Cannabinoid Receptor Modulators
0
Dopamine Agents
0
Lipopolysaccharides
0
Monoterpenes
0
Receptors, Cannabinoid
0
Receptors, Dopamine D2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Fundação de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC), Programa INCT-INOVAMED
ID : Grant no. 465430/2014-7
Pays : International
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