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 (5mg/kg) or sleep-deprived for 24h 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 (50-100mg/kg), (S)-(+)-carvone (50-100mg/kg), and lithium (100mg/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 (100mg/kg), (S)-(+)-carvone (100mg/kg), and lithium also prevented methylphenidate-induced hyperactivity. The present results suggest that carvone may have an antimanic-like effect.