Limonene, a monocyclic terpene is reported to attenuate the stress-induced behavioral manifestations. Stress-induced
release of CRF from hypothalamus is believed to be responsible for anxiogenic- and depressant-like behavior.
Incidentally, limonene is reported to produce anxiolytic- and antidepressant-like effects in rodents. Hypothesizing that
limonene-CRF interaction could be possible reason for its anti-stress effect; to support such possibility, we investigated
the influence of limonene on CRF induced changes in social interaction time in social interaction test, and immobility
time in forced swim test. Results indicated that limonene (50–100 mg/kg, p.o.) or CRF antagonist (1 and 10 ηmol/mouse,
i.c.v.) dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and
antidepressant-like effect. These effects were comparable with the traditional anxiolytic (diazepam, 1–2 mg/kg, i.p.) and
antidepressant (fluoxetine, 10–20 mg/kg, i.p.) agents. CRF (0.01–0.3 ηmol/mouse, i.c.v.) administration produced just
opposite effects to that of limonene on these parameters. Further, limonene (75 or 100 mg/kg, p.o.) pretreatment
antagonized the effects of CRF (0.1 or 0.3 ηmol/mouse, i.c.v.) in social interaction and forced swim test. The subeffective
dose of CRF antagonist (0.1 ηmol/mouse) when administered along with the sub-effective dose of limonene (25
mg/kg) produced significant anxiolytic-and antidepressant-like effect. These observations suggest reciprocating role of
limonene on the CRF-induced anxiogenic- and depressant-like effects.
Limonene, a monocyclic terpene is reported to attenuate the stress-induced behavioral manifestations. Stress-inducedrelease of CRF from hypothalamus is believed to be responsible for anxiogenic- and depressant-like behavior.Incidentally, limonene is reported to produce anxiolytic- and antidepressant-like effects in rodents. Hypothesizing thatlimonene-CRF interaction could be possible reason for its anti-stress effect; to support such possibility, we investigatedthe influence of limonene on CRF induced changes in social interaction time in social interaction test, and immobilitytime in forced swim test. Results indicated that limonene (50–100 mg/kg, p.o.) or CRF antagonist (1 and 10 ηmol/mouse,i.c.v.) dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- andantidepressant-like effect. These effects were comparable with the traditional anxiolytic (diazepam, 1–2 mg/kg, i.p.) andantidepressant (fluoxetine, 10–20 mg/kg, i.p.) agents. CRF (0.01–0.3 ηmol/mouse, i.c.v.) administration produced justopposite effects to that of limonene on these parameters. Further, limonene (75 or 100 mg/kg, p.o.) pretreatmentantagonized the effects of CRF (0.1 or 0.3 ηmol/mouse, i.c.v.) in social interaction and forced swim test. The subeffectivedose of CRF antagonist (0.1 ηmol/mouse) when administered along with the sub-effective dose of limonene (25mg/kg) produced significant anxiolytic-and antidepressant-like effect. These observations suggest reciprocating role oflimonene on the CRF-induced anxiogenic- and depressant-like effects.
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