Background: Major depressive disorder is a psychiatric disorder that affects 4.4% of the
population worldwide. Although the majority of antidepressant drugs ameliorate depressive symptoms,
there is still a need for safer and more effective antidepressant.
Objective: Evaluate the antidepressant-like activity of sesquiterpene compound β-caryophyllene (BCP)
for the possible contribution of the monoamine and hippocampal levels of brain-derived neurotrophic
Methods: Male albino Swiss mice were subjected to the forced swimming test after acute treatment
and to the tail suspension test after repeated treatment. Hippocampal levels of BDNF were assayed by
enzyme-linked immunosorbent assay.
Results: The anti-immobility effect of BCP was reverted by pretreatment with an inhibitor of
catecholamine synthesis α-methyl-p-tyrosine (100 mg/kg, i.p.), α2-adrenergic antagonist yohimbine (1
mg/kg, i.p.), and β-adrenergic antagonist propranolol (2 mg/kg, i.p.), but not by pretreatment with
either α1-adrenergic antagonist prazosin (1 mg/kg, i.p.) or 5-HT1A antagonist NAN-190 (0.5 mg/kg,
i.p.), thereby suggesting the involvement of α2 and β-adrenergic receptors, but not of the α1-adrenergic
and 5-HT1A serotonergic receptors, in BCP's antidepressive-like activity. Furthermore, BCP increased
BDNF levels in the hippocampus after 14 days of treatment. No treatments in this study altered locomotor
activity in the open field test.
Conclusion: This study provides a new mechanism of BCP-induced antidepressant-like effect mediated
by some sub-types of catecholaminergic neurotransmitter system that could be a candidate for
clinical tests of new treatments for depressive disorders.