Methamphetamine modulates ACh-evoked currents in Xenopus occytes expressing the rat alpha7 receptors

Although the cholinergic system is proposed to be involved in methamphetamine (MeAMPH)-induced abnormal behaviors, no direct evidence has been provided yet. The present study investigated the effects of MeAMPH on acetylcholine (ACh)-evoked currents in the neuronal nicotinic ACh receptors (alpha7) expressed in Xenopus oocytes. MeAMPH enhanced the currents in a time- and dose-dependent manner at concentrations ranged from 1 nM to 3 microM, reaching a maximum of 150% 30 min after treatment. Lesser potentiation was observed at higher concentrations (>3 microM) and instead, the currents were inhibited at more than 10 microM MeAMPH with a slow reverse after washing-out of the drug. The current potentiation or depression was caused via a pathway independent of G-protein, protein kinase C or cAMP-dependent protein kinase. The ACh dose-response curve was shifted to the left and to the right after treatment with 1 and 100 microM MeAMPH, respectively, suggesting that MeAMPH potentiated or inhibited ACh-evoked currents by a change in the affinity for ACh. The actions of MeAMPH on the neuronal nicotinic ACh receptors may represent a cellular mechanism for MeAMPH-induced abnormal behaviors and sensitization.