Evidence for the involvement of dopamine in ambulation promoted by menthol in mice

The present study examines the mechanism that underlies the ability of menthol (ME), a major constituent of peppermint oil, to promote mouse ambulation. We initially confirmed that bupropion (BUP), a dopamine (DA) uptake inhibitor, promotes ambulation in ICR mice. Since the subcutaneous administration of ME produced similar effects in mice, we investigated the effects of ME on ambulation when combined with BUP. The results showed that BUP potentiated the effect of ME on mouse ambulation. We then examined effects of the DA antagonists chlorpromazine, haloperidol, fluphenazine, spiperone, and SCH12679 on the ability of BUP and ME to promote ambulation. All of these DA antagonists attenuated the effects of BUP and ME. Prior exposure to reserpine, which depletes monoamines, caused decreased sensitivity to the ability of BUP and of ME in promoting ambulation. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, similarly decreased subsequent sensitivity to the effects of BUP and ME. These results suggest that DA is involved in the abilities of ME and BUP to promote ambulation in mice.