Abstract

The purpose of these studies is to continue to assess the role of free radicals and the toxicity of methamphetamine and MDMA in transgenic and nontransgenic mice. Methamphetamine (METH) is a drug of abuse that causes deleterious effects to brain monoaminergic systems. These toxic effects are thought to be due to oxidative stress. The pineal hormone, melatonin, has been shown to have neuroprotective effects against toxic quinones and oxidative stress produced by catecholamines. The present study was thus undertaken to assess possible protective effects of melatonin against METH-induced neurotoxic effects on the striatum and the nucleus accumbens by using autoradiographic techniques. Four dosages (5, 20, 40, 80 mg/kg) of melatonin were administered to mice intraperitoneally 30 minutes prior to the injections of METH (4 x 5 mg/kg) given at 2- hour intervals. The lowest doses of melatonin (5 mg/kg) had no significant effects against METH-induced toxicity. However, the higher doses (40 or 80 mg/kg) of melatonin significantly attenuated METH- induced toxic effects on both dopamine and serotonin systems. These data provide further evidence for a possible role of oxidative stress in METH-induced toxicity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000153-04
Application #
6103867
Study Section
Special Emphasis Panel (CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

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

  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

Showing the most recent 10 out of 19 publications