Premium
The role of dopamine receptors in the neurotoxicity of methamphetamine
Author(s) -
AresSantos S.,
Granado N.,
Moratalla R.
Publication year - 2013
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12049
Subject(s) - dopamine , dopaminergic , methamphetamine , dopamine transporter , dopamine plasma membrane transport proteins , substantia nigra , dopamine receptor , dopamine receptor d2 , neurotoxicity , pharmacology , dopamine receptor d3 , striatum , medicine , neuroscience , biology , toxicity
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 D 1 or D 2 receptors protects against the loss of dopaminergic fibres in the striatum and loss of dopaminergic neurons in the substantia nigra. Protection by D 1 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 D 2 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.