Methamphetamine modulates ACh-evoked currents in Xenopus oocytes expressing the rat α7 receptors

• Published in: Neuroscience letters Vol. 239; no. 2; pp. 73 - 76
• Main Authors: Nomura, Tamotsu, Nishizaki, Tomoyuki
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15-12-1997; Elsevier
• Subjects: ACh; Biological and medical sciences; Medical sciences; Methamphetamine; Neuronal α7 receptor; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Voltage-clamp; Xenopus oocyte; Neuronal α7 receptor; Voltage-clamp; ACh; Xenopus oocyte; Methamphetamine; Amphetamine derivatives; Rat; CNS stimulant; Rodentia; Metamfetamine; Ionic current; In vitro; Cholinergic receptor; Vertebrata; Mammalia; Animal; Neurotransmitter; Acetylcholine; Sensitization; Mechanism of action; Nicotinic receptor
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(97)00911-7

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 (
α7) expressed in
Xenopus oocytes. MeAMPH enhanced the currents in a time- and dose-dependent manner at concentrations ranged from 1 nM to 3
μM, reaching a maximum of 150% 30 min after treatment. Lesser potentiation was observed at higher concentrations (>3
μM) and instead, the currents were inhibited at more than 10
μM 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
μM 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.