Toxicity of Amphetamine Analogs

Cadet, J L.

Abstract

The purpose of these studies is to continue to evaluate the toxic effects of MDMA and METH (Ecstasy) in SOD-Transgenic mice. The subacute and long-term biochemical effects of methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) were assessed in homozygous and heterozygous transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene. Non-transgenic (NON-Tg) mice showed significant decreases in striatal dopamine (DA) and dihydroxyphenylacetic acid (50 mg/kg) after MDMA treatment. Heterozygous SOD-Tg mice showed DA depletion only at the 354 h time point. In contrast, homozygous SOD-Tg mice showed no DA or DOPAC depletion at either the 24 h or at the 2 week time points. METH injections caused marked depletion of dopamine terminals in wild- type mice. However, both heterozygous and homozygous SOD-Tg mice showed protection against the toxic effects of METH with the homozygous animals showing the greatest protection. These results support previous observations that MDMA-induces biochemical in the 5-HT systems of rats. The present observations also document a role for the production of superoxide radicals in the effects of both MDMA and METH. These mice are an important tool for dissecting pathways involved in drug-induced neurotoxicity.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Drug Abuse (NIDA)
• Type: Intramural Research (Z01)
• Project #: 1Z01DA000153-02
• Application #: 2571609
• Study Section: Special Emphasis Panel (NS)
• Support Year: 2
• Fiscal Year: 1996

Institution

• Name: National Institute on Drug Abuse
• Country: United States

Publications

Wang, Yun; Chang, Chen-Fu; Chou, Jenny et al. (2005) Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol 193:75-84

Chen, Jia; Lee, Chun-Ting; Errico, Stacie et al. (2005) Protective effects of Delta(9)-tetrahydrocannabinol against N-methyl-d-aspartate-induced AF5 cell death. Brain Res Mol Brain Res 134:215-25

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

Bolla, K I; Eldreth, D A; London, E D et al. (2003) Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. Neuroimage 19:1085-94

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

Contoreggi, Carlo; Herning, Ronald I; Na, Paul et al. (2003) Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease. Biol Psychiatry 54:873-8

Lyles, Johnalyn; Cadet, Jean Lud (2003) Methylenedioxymethamphetamine (MDMA, Ecstasy) neurotoxicity: cellular and molecular mechanisms. Brain Res Brain Res Rev 42:155-68