Antimanic-like effects of (R)-(-)-carvone and (S)-(+)-carvone in mice

Carvone is a monoterpene that is present in spearmint (Mentha spicata) and caraway (Carum carvi) essential oils and has been shown to have anticonvulsant effects, likely through the blockade of voltage-gated sodium channels, and anxiolytic-like effects. Considering that some anticonvulsants that blocked voltage gated sodium channels (e.g., sodium valproate and carbamazepine) exert clinical antimanic effects, the aim of the present study was to evaluate (R)-(-)-carvone and (S)-(+)-carvone in animal models of mania (i.e., hyperlocomotion induced by methylphenidate and sleep deprivation). Mice that were treated with methylphenidate (5 mg/kg) or sleep-deprived for 24 h using a multiple-platform protocol exhibited an increase in locomotor activity in an automated activity box. This effect was blocked by pretreatment with acute (R)(-)-carvone (50-100 mg/kg), (S)-(+)-carvone (50-100 mg/kg), and lithium (100 mg/kg, positive control). These doses did not alter spontaneous locomotor activity in the methylphenidate-induced experiments while (S)-(+)-carvone decreased spontaneous locomotor activity in sleep deprivation experiment, indicating a sedative effect. Chronic 21-day treatment with (R)-(-)-carvone (100 mg/kg), (S)-(+)-carvone (100 mg/kg), and lithium also prevented methylphenidate-induced hyperactivity. The present results suggest that carvone may have an antimanic-like effect. (C) 2016 Elsevier Ireland Ltd. All rights reserved.