Abstract

Amphetamine (AMPH) is a drug of abuse that causes the degeneration of striatal dopamine terminals in mammals. Superoxide radicals seem to participate in AMPH-induced damage because its toxicity is attenuated in Cu/Zn superoxide dismutase transgenic (SOD-tg) mice. To provide a detailed analysis of molecular changes associated with AMPH toxicity, we used cDNA arrays consisting of 1176 genes to detect differential changes in gene expression in the striata of wild-type and SOD-tg mice treated with neurotoxic doses of the drug. We found 42 genes that showed >1.8-fold changes in at least two consecutive time points during the course of the study and were differentially affected by AMPH in the two genotypes. Specifically, more transcription factors and genes involved in responses to injury/inflammation were affected in wild-type mice after AMPH administration. Some of these stimulant-induced superoxide-dependent alterations in gene expression might affect neuronal functions and promote neuronal damage. Other changes might help to provide some degree of protection against AMPH toxicity. These results support the view that the use of global array analysis of gene expression will help to identify novel molecular mediators of AMPH-induced neurodegeneration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000174-09
Application #
6827533
Study Section
(CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Atianjoh, Fidelis E; Ladenheim, Bruce; Krasnova, Irina N et al. (2008) Amphetamine causes dopamine depletion and cell death in the mouse olfactory bulb. Eur J Pharmacol 589:94-7
Deng, Xiaolin; Ladenheim, Bruce; Jayanthi, Subramaniam et al. (2007) Methamphetamine administration causes death of dopaminergic neurons in the mouse olfactory bulb. Biol Psychiatry 61:1235-43
Sokolov, Boris P; Cadet, Jean L (2006) Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness. Neuropsychopharmacology 31:956-66
Cai, Ning Sheng; McCoy, Michael T; Ladenheim, Bruce et al. (2006) Serial analysis of gene expression in the rat striatum following methamphetamine administration. Ann N Y Acad Sci 1074:13-30
Krasnova, Irina N; Ladenheim, Bruce; Cadet, Jean Lud (2005) Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway. FASEB J 19:851-3
Jayanthi, Subramaniam; Deng, Xiaolin; Noailles, Pierre-Antoine H et al. (2004) Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades. FASEB J 18:238-51
Sokolov, Boris P; Schindler, Charles W; Cadet, Jean Lud (2004) Chronic methamphetamine increases fighting in mice. Pharmacol Biochem Behav 77:319-26
Yu, Jing; Wang, Jing; Cadet, Jean Lud et al. (2004) Histological evidence supporting a role for the striatal neurokinin-1 receptor in methamphetamine-induced neurotoxicity in the mouse brain. Brain Res 1007:124-31
Rothman, Richard B; Jayanthi, Subramaniam; Wang, Xiaoying et al. (2003) High-dose fenfluramine administration decreases serotonin transporter binding, but not serotonin transporter protein levels, in rat forebrain. Synapse 50:233-9
Noailles, Pierre Antoine H; Becker, Kevin G; Wood 3rd, William H et al. (2003) Methamphetamine-induced gene expression profiles in the striatum of male rat pups exposed to the drug in utero. Brain Res Dev Brain Res 147:153-62

Showing the most recent 10 out of 16 publications