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Article

Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor

1
Laboratory of Autoimmunity and Immunopharmacology (LAIF), Department of Health Sciences, Campus Araranguá, Universidade Federal de Santa Catarina, Araranguá 88906-072, Brazil
2
Post-Graduate Program of Neuroscience, Center of Biological Science, Campus Florianópolis, Universidade Federal de Santa Catarina, Florianópolis 88040-900, Brazil
3
Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
4
Laboratory of Neurobiology of Pain and Inflammation, Department of Physiological Sciences, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, Brazil
5
Center for Research and Innovation in Health Sciences (NUPICS), Faculty of Pharmacy, Universidade Federal de Juiz de Fora, Juiz de For a 36036-330, Brazil
6
Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
7
Endocannabinoid Research Group, 80078 Naples, Italy
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(5), 792; https://doi.org/10.3390/biom10050792
Received: 21 April 2020 / Revised: 13 May 2020 / Accepted: 15 May 2020 / Published: 20 May 2020
(This article belongs to the Collection Pharmacology of Medicinal Plants)
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. View Full-Text
Keywords: depression; terpenoids; phytocannabinoid; cannabinoid receptor; dopaminergic receptor depression; terpenoids; phytocannabinoid; cannabinoid receptor; dopaminergic receptor
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MDPI and ACS Style

Vieira, G.; Cavalli, J.; Gonçalves, E.C.D.; Braga, S.F.P.; Ferreira, R.S.; Santos, A.R.S.; Cola, M.; Raposo, N.R.B.; Capasso, R.; Dutra, R.C. Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor. Biomolecules 2020, 10, 792. https://doi.org/10.3390/biom10050792

AMA Style

Vieira G, Cavalli J, Gonçalves ECD, Braga SFP, Ferreira RS, Santos ARS, Cola M, Raposo NRB, Capasso R, Dutra RC. Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor. Biomolecules. 2020; 10(5):792. https://doi.org/10.3390/biom10050792

Chicago/Turabian Style

Vieira, Graziela, Juliana Cavalli, Elaine C.D. Gonçalves, Saulo F.P. Braga, Rafaela S. Ferreira, Adair R.S. Santos, Maíra Cola, Nádia R.B. Raposo, Raffaele Capasso, and Rafael C. Dutra. 2020. "Antidepressant-Like Effect of Terpineol in an Inflammatory Model of Depression: Involvement of the Cannabinoid System and D2 Dopamine Receptor" Biomolecules 10, no. 5: 792. https://doi.org/10.3390/biom10050792

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