Posted by West on January 1, 2010, at 9:19:01
In reply to Re: Is Amphetamine Neurotoxic? question, posted by Rosy Crucifiction on November 27, 2009, at 13:01:37
In mice and rats
Long-lasting dopamine receptor up-regulation in previous amphetamine treated rats following previous amphetamine neurotoxicity
Jeremy Z. Fieldsa, b, Lawrence Wichlinskia, b, George E. Druckera, b, Kevin Engha, b and John H. Gordona, baResearch Service (151), Hines V. A. Hospital, Hines, IL 60141, USA
bDepartment of Pharmacology, Loyola University Stritch School of Medicine 2160 S. First Ave., Maywood, IL 60153, USA
Received 4 June 1991.
Available online 22 January 2003.Abstract
previous Amphetamine term (A) (9.2 mg/kg, IP), in combination with iprindole (I) (10.0 mg/kg, IP), caused long-lasting previous dopamine term (DA) previous depletions in striatum (−49%, 4 weeks) but not in nucleus accumbens following one A/I injection. Striatal DA had recovered by 4 months. DA receptors (DAr) were up-regulated: 1) behavioral responses to a DA receptor agonist (apomorphine) were significantly elevated. These included apomorphine-induced locomotor activity (+ 103% and + 160%, on weeks 3 and 10) and apomorphine-induced stereotypy (day 10). 2) Bmax for [3H]spiroperidol binding to striatal D2 DAr (12 weeks) increased (+53%, week 12.). Injection of the DAr neuromodulator cyclo(leucyl-glycyl) (8 mg/kg/day × 4 days, SC) reversed the Bmax increase. Thus toxicity (DA previous depletion)next term following high-dose previous amphetamine appears to induce compensatory changes in DAr. This DAr upregulation may explain the lack of abnormal movements despite enduring DA previous depletion.Additionally, the A/I paradigm as an animal model of long-lasting DAr up-regulation, could be used to screen neuromodulatory agents, like CLG, that might treat disorders (e.g., tardive dyskinesia and schizophrenia) thought to involve up-regulated DAr.
Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2
Purchase the full-text articleEvan L. RiddleCorresponding Author Contact Information, a, E-mail The Corresponding Author, Glen R. Hansona and Annette E. Fleckensteina
aDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112
Received 12 January 2007;
revised 17 May 2007;
accepted 22 May 2007.
Available online 5 June 2007.Abstract
High-dose administration of psychostimulants traffics the vesicular monoamine transporter-2 (VMAT-2), as assessed by subcellular fractionation of rat striatal tissue. This study demonstrates that administration of low doses of amphetamine or methylphenidate differentially traffic VMAT-2 within nerve terminals, with effects similar to those observed after high-dose administration. Trafficking of vesicular glutamate, acetylcholine, or GABA transporters was not altered by high-or low-dose amphetamine or methylphenidate treatment. These data represent the first report that amphetamine redistributes VMAT-2 protein. In addition, these data demonstrate that the trafficking of VMAT-2 after amphetamine or methylphenidate is selective for monoaminergic neurons.
http://www.ncbi.nlm.nih.gov/pubmed/7301203
Continuous administration of D-amphetamine to mice by osmotic minipumps (placed s.c.) delivering 25 micrograms/h for 7 days led to significant decreases in the endogenous dopamine concentration (-51%) and [3H]noradrenaline uptake (-43%) in vitro in the caudate nucleus. Fluorescence histochemical analysis demonstrated a marked reduction of dopamine fluorescence as well as catecholamine accumulations (sign of neurotoxicity) in the caudate nucleus. No notable effects were noted on the fluorescence morphology of the dopamine cell bodies in the mesencephalon. The dopamine levels were still significantly reduced (-37%) after two months, while the [3H]noradrenaline uptake had at this time-point reached almost normal values. The results are compatible with the view that D-amphetamine can induce acutely a neurodegenerative damage of central dopamine neurons at the level of the nerve terminals in the caudate nucleus with possibilities for regeneration and recovery in the chronic state.Science. 1978 Jul 21;201(4352):276-8.
Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration.Ellison G, Eison MS, Huberman HS, Daniel F.
Silicone pellets containing d-amphetamine base were implanted subcutaneously in rats. These pellets release amphetamine continuously for at least 10 days. Several days after implantation, swollen dopamine axons concomitant with large decreases in tyrosine hydroxylase activity were observed in the caudate nucleus. Decreased tyrosine hydroxylase activity was still present 110 days after pellet removal in the caudate but not in several other brain regions, nor in the caudate of rats injected with an equivalent amount of amphetamine in daily injections. This implies that continuous amphetamine administration has a selective neurotoxic effect on dopamine terminals in the caudate.
Methylphenidate and brain dopamine neurotoxicity
Purchase the full-text articleReferences and further reading may be available for this article. To view references and further reading you must purchase this article.
Jie Yuana, *, Una McCannb and George Ricaurtea
a Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA
b Unit on Anxiety Disorders, Biological Psychiatry Branch, NIMH, Bethesda, MD 20892, USA
Accepted 10 June 1997.
Available online 20 November 1997.
AbstractTo further evaluate the dopamine (DA) neurotoxic potential of the widely prescribed psychostimulant, methylphenidate, mice were treated with various doses (range: 10120 mg/kg) and treatment schedules of methylphenidate (every 2 h×4 or twice daily×4). Higher doses of methylphenidate produced intense stereotypy, as well as short- (5-day), but not long- (2-week), term depletions of striatal DA axonal markers. By contrast, amphetamine caused not only intense stereotypy, but also profound, long-lasting, dose-related DA deficits. These findings indicate that results of studies of amphetamine neurotoxicity using short (5-day) post-drug survival periods are potentially misleading. Further, the present findings confirm and extend previous results indicating that methylphenidate, unlike amphetamine, lacks DA neurotoxic potential, and strongly suggest that DA efflux, although perhaps necessary, is not sufficient for the expression of amphetamine-induced DA neurotoxicity.
poster:West
thread:926522
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