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Curr Mol Pharmacol ; 14(1): 36-51, 2021.
Article in English | MEDLINE | ID: mdl-32386503

ABSTRACT

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 ß-caryophyllene is still little discussed. OBJECTIVES: One of the objectives of the present study was to demonstrate the anxiolytic behavioral effect of ß-caryophyllene (ß-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 ß-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 ß-CBP may involve benzodiazepine/GABAergic receptors, since the pre-treatment of ß-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 ß-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 ß-CBP. CONCLUSION: The results obtained provide additional support in understanding the neuromolecular mechanisms underlying the anxiolytic, antidepressant and anticonvulsive properties of ß-CBP in female Swiss mice.


Subject(s)
Anti-Anxiety Agents/chemistry , Anticonvulsants/chemistry , Antidepressive Agents/chemistry , GABA-A Receptor Antagonists/chemistry , Polycyclic Sesquiterpenes/chemistry , Animals , Anti-Anxiety Agents/pharmacology , Anticonvulsants/pharmacology , Antidepressive Agents/pharmacology , Arginine , Behavior, Animal , Benzodiazepines/metabolism , Bicuculline/chemistry , Bicuculline/pharmacology , Female , Flumazenil/chemistry , Flumazenil/pharmacology , GABA-A Receptor Antagonists/pharmacology , Humans , Maze Learning , Mice , Nitric Oxide/metabolism , Polycyclic Sesquiterpenes/pharmacology , Receptors, GABA-A/metabolism , Seizures/chemically induced , Signal Transduction
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