The Role of Oxidative Stress in Methamphetamine-induced Toxicity and Sources of Variation in the Design of Animal Studies.
BACKGROUND
The prevalence of methamphetamine (MA) use has increased in recent years. In order to assess how this drug produces its effects, both clinical and preclinical studies have recently begun to focus on oxidative stress as an important biochemical mechanism in mediating these effects.


OBJECTIVE
The purpose of this review is to illustrate the variation in the design of preclinical studies investigating MA exposure on oxidative stress parameters in animal models.


METHODS
The experimental variables investigated and summarised include MA drug treatment, measurements of oxidative stress and antioxidant treatments that ameliorate the harmful effects of MA.


RESULTS
These preclinical studies differ greatly in their experimental design with respect to the dose of MA (ranging between 0.25 and 20 mg/kg), the dosing regime (acute, binge or chronic), the time of measurement of oxidative stress (0.5 h to 2 wks after last MA administration), the antioxidant system targeted and finally the use of antioxidants including the route of administration (i.p. or p.o.), the frequency of exposure and the time of exposure (preventative or therapeutic).


CONCLUSIONS
The findings in this paper suggest that there is a large diversity among these studies and so the interpretation of these results is challenging. For this reason, the development of guidelines and how best to assess oxidative stress in animal models may be beneficial. The use of these simple recommendations mean that results will be more comparable between laboratories and that future results generated will give us a greater understanding of the contribution of this important biochemical mechanism and its implications for the clinical scenario.
Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Galway, Ireland.
Kate
K
McDonnell-Dowling
John P
JP
Kelly
D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D008694:Methamphetamine