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Anticonvulsant, Anxiolytic and Antidepressant Properties of the β-caryophyllene in Swiss Mice: Involvement of Benzodiazepine-GABAAergic, Serotonergic and Nitrergic Systems


George Laylson da Silva Oliveira*, José Carlos Correia Lima da Silva, Ana Paula dos Santos C. L da Silva, Chistiane Mendes Feitosa and Fernanda Regina de Castro Almeida   Pages 1 - 16 ( 16 )


Background: Central nervous system disorders such as anxiety, depression and epilepsy are characterized by sharing several molecular mechanisms in common and the involvement of the L-arginine/NO pathway in neurobehavioral studies with β-caryophyllene is still little discussed.

Objectives: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of β-caryophyllene (β-CBP) in female Swiss mice, as well as to investigate the molecular mechanisms underlying the results obtained.

Methods: This study evaluated the neurobehavioral effects of β-CBP using the open field test, rota-rod test, elevated plus maze test, novelty suppressed feeding test, tail suspension test and forced swim test, as well as pilocarpine, pentylenetetrazole and isoniazid-induced epileptic seizure models.

Results: The results demonstrated that the neuropharmacological activities of β-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of β-CBP (200 mg/kg) associated with flumazenil (5 mg/kg, benzodiazepine receptor antagonist) and bicuculline (1 mg/kg, selective GABAA receptor antagonist) reestablished the anxiety parameters in the elevated plus-maze test, as well as the results of reduced latency to consume food in the novelty suppressed feeding test. In addition to benzodiazepine/GABAergic receptors, the neuropharmacological properties of β-CBP may be related to inhibition of nitric oxide synthesis, since pre-treatment with L-arginine (500- 750 mg/kg) reversed significantly the anxiolytic, antidepressant and anticonvulsant activities of β-CBP.

Conclusion: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of β-CBP in female Swiss mice.


β-caryophyllene, benzodiazepine/GABAergic receptors, neurobehavioral effects, neuromolecular mechanisms, nitric oxide, L-arginine/NO pathway.


Department of Biology, Federal Institute of Mato Grosso, Guarantã do Norte - MT, 78520-000, Guarantã do Norte Campus, Laboratory of Education and Research in Toxicology and Pharmacology (LEPTOX-F); bDepartment of Computer Science, Federal University of Piaui, Teresina, 64049-550, Piaui, Department of Pharmacy, Federal University of Piauí, 64049-550, Teresina, Department of Chemistry, University Federal of Piauí, 64049-550, Teresina, Center for Research on Medicinal Plants, Federal University of Piauí, 64049-550 Teresina

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