These authors contributed equally.
The role of dopamine receptors in the neurotoxicity of methamphetamine
Article first published online: 22 APR 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 273, Issue 5, pages 437–453, May 2013
How to Cite
Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC, Madrid; CIBERNED, ISCIII, Madrid; Universidad Complutense de Madrid, Madrid, Spain The role of dopamine receptors in the neurotoxicity of methamphetamine. J Intern Med 2013; 273: 437–453., , .
- Issue published online: 22 APR 2013
- Article first published online: 22 APR 2013
- Spanish Ministry of Ciencia e Innovación. Grant Number: BFU2010-20664
- Spanish Ministries of Economía y Competitividad and of Sanidad, Servicios Socales e Igualdad, ISCIII, PNSD RedRTA. Grant Number: RD06/0001/1011
- CIBERNED. Grant Number: CB06/05/0055
- Comunidad de Madrid. Grant Number: S2011/BMD-2336
- amphetamine derivatives;
- designer drugs;
- drug addiction;
- Parkinson's disease;
Methamphetamine is a synthetic drug consumed by millions of users despite its neurotoxic effects in the brain, leading to loss of dopaminergic fibres and cell bodies. Moreover, clinical reports suggest that methamphetamine abusers are predisposed to Parkinson's disease. Therefore, it is important to elucidate the mechanisms involved in methamphetamine-induced neurotoxicity. Dopamine receptors may be a plausible target to prevent this neurotoxicity. Genetic inactivation of dopamine D1 or D2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D1 receptor inactivation is due to blockade of hypothermia, reduced dopamine content and turnover and increased stored vesicular dopamine in D1R−/− mice. However, the neuroprotective impact of D2 receptor inactivation is partially dependent on an effect on body temperature, as well as on the blockade of dopamine reuptake by decreased dopamine transporter activity, which results in reduced intracytosolic dopamine levels in D2R−/− mice.