Origanum majorana (
L
.)
is an herb used in the treatment of diseases related to the nervous system in traditional medicine (e.g. as an anticonvulsant and sedative). The present study was conducted to investigate the antidepressant-like effects of
Origanum majorana
essential oil (OMEO) on mice in the forced swimming test (FST). The animals were intraperitoneally (i.p.) injected with OMEO (10–80 mg/kg) 1 h before the FST. To assess the involvement of the monoaminergic system in the antidepressant activity of OMEO, different pharmacological antagonists were administered 15 min before OMEO administration (80 mg/kg). The administration of OMEO (40 and 80 mg/kg, i.p.) decreased immobility time and increased swimming and climbing times significantly. OMEO did not cause any changes in spontaneous locomotor function in the open-field test (OFT). The pre-treatment of the animals with SCH23390, sulpiride, haloperidol, WAY100135,
p
-chlorophenylalanine (pCPA), ketanserin, prazosin, yohimbine, reserpine, but
not
propranolol, inhibited the anti-immobility effect of OMEO in the FST. A combination of sub-effective doses of fluoxetine (5 mg/kg, i.p.) or imipramine (5 mg/kg, i.p.) with OMEO (10 mg/kg, i.p.) increased the antidepressant-like effects. OMEO showed antidepressant-like effects through involvement with the dopaminergic (D
1
and D
2
), serotonergic (5HT1
A
, 5-HT2
A
receptors) and noradrenergic (α
1
and α
2
adrenoceptors) systems.
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