"Gene Haywood" <gehayw at hotmail.com> wrote in message
news:bd56540c.0305272059.7bdad0a9 at posting.google.com...
> Are there any studies that indicate a greater susceptability to
> Parkinson's disease(presumably a result of dopaminergic injury) on the
> part of former or current amphetamine abusers?
Don't know but I think there is some anecdotal evidence re extreme cocaine
abuse and P. had a quick look, nothing substantial but wouldn't surprise me.
Your idea makes sense, to the extent that anything in Neuroscience makes
sense ... . Dopamine neurons are v. sensitive to ROS and BG high in iron
(potentiates ROS via Fenton) and also high concentrations of microglia I
think. Damn I hate this.
Neurotoxicology 2001 Dec;22(6):725-31Related Articles,
Is methamphetamine abuse a risk factor in parkinsonism?
Department of Environmental Health Sciences, School of Hygiene and Public
Health, The Johns Hopkins University, Baltimore, MD 21205, USA
Parkinsons disease (PD) is a neurodegenerative disorder with increased
incidence in individuals beyond 50 years of age. The etiology of PD is
currently not known, but it appears that environmental factors may play an
important role. The molecular basis of PD is the nearly complete loss of the
neurotransmitter dopamine (DA) in the basal ganglia (caudate/putamen). The
decrease in dopamine levels is the result of degeneration of
dopamine-containing neurons in the substantia nigra. This biochemical
deficit in the nigrostriatal pathway leads to the emergence of motor
impairments typical of PD. Methamphetamine (METH) is a psychostimulant drug
with increasing use in certain segments of the population in the United
States and worldwide. In experimental animal models and human studies, METH
administration has been shown to decrease markers of dopaminergic neuron
terminal integrity in the basal ganglia. A long-standing question has been
whether the reductions in dopaminergic markers induced by METH constitute
degenerative changes or reflect drug-induced modulation. Resolving this
question is important because the irreversible loss of dopaminergic function
may increase the likelihood of Parkinsonism with advancing age.
· Review, Tutorial
PMID: 11829406 [PubMed - indexed for MEDLINE]
Ann N Y Acad Sci 2002 Jun;965:225-32Related Articles,The protective role of
L-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine,
could be related to mitochondrial dysfunction.
Virmani A, Gaetani F, Imam S, Binienda Z, Ali S.
Research and Development, Sigma tau-HealthScience, Pomezia 00040, Italy.
There is growing evidence that suggests that brain injury after amphetamine
and methamphetamine (METH) administration is due to an increase in free
radical formation and mitochondrial damage, which leads to a failure of
cellular energy metabolism followed by a secondary excitotoxicity. Neuronal
degeneration caused by drugs of abuse is also associated with decreased ATP
synthesis. Defective mitochondrial oxidative phosphorylation and metabolic
compromise also play an important role in atherogenesis, in the pathogenesis
of Alzheimer's disease, Parkinson's disease, diabetes, and aging. The energy
deficits in the central nervous system can lead to the generation of
reactive oxygen and nitrogen species as indicated by increased activity of
the free radical scavenging enzymes like catalase and superoxide dismutase.
The METH-induced dopaminergic neurotoxicity may be mediated by the
generation of peroxynitrite and can be protected by antioxidants selenium,
melatonin, and selective nNOS inhibitor, 7-nitroindazole. L-Carnitine (LC)
is well known to carry long-chain fatty acyl groups into mitochondria for
beta-oxidation. It also plays a protective role in 3-nitropropioinc acid
(3-NPA)-induced neurotoxicity as demonstrated in vitro and in vivo. LC has
also been utilized in detoxification efforts in fatty acid-related metabolic
disorders. In this study we have tested the hypothesis that enhancement of
mitochondrial energy metabolism by LC could prevent the generation of
peroxynitrite and free radicals produced by METH. Adult male C57BL/6N mice
were divided into four groups. Group I served as control. Groups III and IV
received LC (100 mg/kg, orally) for one week. Groups II and IV received 4 x
10 mg/kg METH i.p. at 2-h intervals after one week of LC administration. LC
treatment continued for one more week to groups III and IV. One week after
METH administration, mice were sacrificed by decapitation, and striatum was
dissected to measure the formation of 3-nitrotyrosine (3-NT) by
HPLC/Coularry system. METH treatment produced significant formation of 3-NT,
a marker of peroxynitrite generation, in mice striatum. The pre- and
post-treatment of mice with LC significantly attenuated the production of
3-NT in the striatum resulting from METH treatment. The protective effects
by the compound LC in this study could be related to the prevention of the
possible metabolic compromise by METH and the resulting energy deficits that
lead to the generation of reactive oxygen and nitrogen species. These data
further confirm our hypothesis that METH-induced neurotoxicity is mediated
by the production of peroxynitrite, and LC may reduce the peroxynitrite
levels and protect against the underlying mechanism of METH toxicity, which
are models for several neurodegenerative disorders like Parkinson's disease.