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. Several genes showed changes that were superoxide-dependent. We are characterizing the effects of AMPH on gene expression in the cortex.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000174-16
Application #
8148490
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2010
Total Cost
$123,662
Indirect Cost

  Institution

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

  Publications

Pogorelov, Vladimir M; Nomura, Jun; Kim, Jongho et al. (2012) Mutant DISC1 affects methamphetamine-induced sensitization and conditioned place preference: a comorbidity model. Neuropharmacology 62:1242-51
Krasnova, Irina N; Ladenheim, Bruce; Hodges, Amber B et al. (2011) Chronic methamphetamine administration causes differential regulation of transcription factors in the rat midbrain. PLoS One 6:e19179
Thiriet, Nathalie; Agasse, Fabienne; Nicoleau, Camille et al. (2011) NPY promotes chemokinesis and neurogenesis in the rat subventricular zone. J Neurochem 116:1018-27
Schwilke, Eugene W; Gullberg, Rod G; Darwin, William D et al. (2011) Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction 106:499-506
Cadet, Jean Lud; Brannock, Christie; Ladenheim, Bruce et al. (2011) Methamphetamine preconditioning causes differential changes in striatal transcriptional responses to large doses of the drug. Dose Response 9:165-81
Ayhan, Y; Abazyan, B; Nomura, J et al. (2011) Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders. Mol Psychiatry 16:293-306
McCoy, Michael T; Jayanthi, Subramaniam; Wulu, Jacqueline A et al. (2011) Chronic methamphetamine exposure suppresses the striatal expression of members of multiple families of immediate early genes (IEGs) in the rat: normalization by an acute methamphetamine injection. Psychopharmacology (Berl) 215:353-65
Rothman, Richard B; Cadet, Jean L; Dersch, Christina M et al. (2011) Altered gene expression in pulmonary tissue of tryptophan hydroxylase-1 knockout mice: implications for pulmonary arterial hypertension. PLoS One 6:e17735
Shin, Eun-Joo; Duong, Chu Xuan; Nguyen, Xuan-Khanh Thi et al. (2011) PKC? inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment. Neurochem Int 59:39-50
Scheidweiler, Karl B; Ladenheim, Bruce; Cadet, Jean Lud et al. (2010) Mice lacking multidrug resistance protein 1a show altered dopaminergic responses to methylenedioxymethamphetamine (MDMA) in striatum. Neurotox Res 18:200-9

Showing the most recent 10 out of 18 publications