A single dose model of methamphetamine-induced neurotoxicity in rats: effects on neostriatal monoamines and glial fibrillary acidic protein

Fukumura, Masao; Cappon, Gregg D.; Pu, Cunfeng; Broening, Harry W.; Vorhees, Charles V.

doi:10.1016/s0006-8993(98)00656-8

Cited by 100 publications

(78 citation statements)

References 18 publications

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“…Furthermore, the results of the present experiment, in which the number of C-tau immunoreactive cells has been shown to be increased in the striatum following METH or AMPH treatment, but not MDMA or PMA treatment, are in agreement with previous studies that have examined GFAP immunoreactivity or protein expression. Treatment of rodents with a METH regimen similar to that used in this study or single high-dose METH administration has been reported to produce an increase in GFAP in the striatum as measured by semiquantitative immunoblot (Fukumura et al, 1998) or immunoreactivity (Bowyer et al, 1994, Broening et al, 1997 3 days after drug treatment. Various dosing regimens of AMPH also have been reported to increase striatal GFAP immunoreactivity (Bowyer, 2000, Armstrong et al, 2004, Bowyer et al, 2004.…”

Section: Discussionmentioning

confidence: 85%

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

et al. 2007

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The present study quantified the cleaved form of the microtubule associated protein tau (cleaved MAP-tau, C-tau), a previously demonstrated marker of CNS toxicity, following the administration of monoamine-depleting regimens of the psychostimulant drugs amphetamine (AMPH), methamphetamine (METH), ±3,4-methylenedioxymethamphetamine (MDMA), or paramethoxyamphetamine (PMA) in an attempt to further characterize psychostimulant-induced toxicity. A dopamine (DA)-depleting regimen of AMPH produced an increase in C-tau immunoreactivity in the striatum, while a DA-and serotonin (5-HT)-depleting regimen of METH produced an increase in the number of C-tau immunoreactive cells in the striatum and CA2/CA3 and dentate gyrus regions of the hippocampus. MDMA and PMA, two psychostimulant drugs that produce selective 5-HT depletion in the striatum, had no effect on C-tau immunoreactivity in the striatum or hippocampus. Furthermore, 5,7-dihydroxytryptamine (5,7-DHT), an established 5-HT selective neurotoxin, did not produce an increase in C-tau immunoreactivity. Dual fluorescent immunocytochemistry with antibodies to GFAP and C-tau indicated that C-tau immunoreactivity was present in astrocytes, not neurons, suggesting that increased C-tau may be an alternative indicator of reactive gliosis. The present results are consistent with previous findings that the DA-depleting psychostimulants AMPH and METH produce reactive gliosis whereas the 5-HT-depleting drugs MDMA and PMA, as well as the known 5-HT selective neurotoxin 5,7-DHT, do not produce an appreciable glial response. Keywords methamphetamine; 3,4-methylenedioxymethamphetamine; amphetamine; paramethoxyamphetamine; 5,7-dihydroxytryptamine; toxicity Methamphetamine (METH) and ±3,4-methylenedioxymethamphetamine (MDMA) are substituted phenylethylamines whose popularity among young adults continues to be a public

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Section: Discussionmentioning

confidence: 85%

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

et al. 2007

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“…However, both are as effective inducing deficits of DA terminal markers in the striatum of mice [42,43,44]. Both dose schedules of METH induce GFAP in striatal astrocytes [12]. However, a study suggests that this astrocytic response may be due to degenerating corticostriatal fibers since GFAP induction was observed in the absence of depletion of striatal TH [24].…”

Section: Discussionmentioning

confidence: 99%

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

Zhu

Angulo

2005

Brain Research

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Methamphetamine (METH) causes damage in the striatum at pre-and post-synaptic sites. Exposure to METH induces long-term depletions of dopamine (DA) terminal markers such as tyrosine hydroxylase (TH) and DA transporters (DAT). METH also induces neuronal apoptosis in some striatal neurons. The purpose of this study is to demonstrate which occurs first, apoptosis of some striatal neurons or DA terminal toxicity in mice. This is important because the death of striatal neurons leaves the terminals in a state of deafferentation. A bolus injection (i.p.) of METH (30 mg/kg) induces apoptosis (TUNEL staining) in approximately 25% of neurons in the striatum at 24 h after METH. However, in contrast to apoptosis, depletion of TH (Western blotting) begins to appear at 24 h after METH in dorsal striatum while the ventral striatum is unaffected. The peak of TH depletion (approximately 80% decrease relative to control) occurs at 48 h after METH. Autoradiographic analysis of DAT sites showed that depletion begins to appear 24 h after METH and peaks at 2 days (approximately 60% depletion relative to control). Histological analysis of the induction of glial fibrillary acidic protein (GFAP) by METH in striatal astrocytes revealed an increase at 48 h after METH that peaked at 3 days. These data demonstrate that striatal apoptosis precedes the depletion (toxicity) of DA terminal markers in the striatum of mice, suggesting that the ensuing state of deafferentation of the DA terminals may contribute to their degeneration.

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“…In particular, animals given repeated doses of METH develop long-lasting depletions of DA and 5-HT, their major metabolites, their membrane transporters, their rate-limiting biosynthetic enzymes, and their vesicular transporters (Gibb et al, 1994;Lew et al, 1997;Cho and Melega, 2002;McCann and Ricaurte, 2004). Anatomic studies indicate that reductions in presynaptic DA and 5-HT axonal markers are related to destruction of DA and 5-HT axon terminals (Ricaurte et al, 1982(Ricaurte et al, , 1984aSonsalla et al, 1996, Fukumura et al, 1998.…”

Section: Methamphetaminementioning

confidence: 99%

Relationship between Temperature, Dopaminergic Neurotoxicity, and Plasma Drug Concentrations in Methamphetamine-Treated Squirrel Monkeys

Yuan

Hatzidimitriou

Suthar

et al. 2005

J Pharmacol Exp Ther

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To examine the relationship between temperature (ambient and core), dopaminergic neurotoxicity, and plasma drug [methamphetamine (METH)] and metabolite [amphetamine (AMPH)] concentrations, two separate groups of squirrel monkeys (n ϭ 4 -5 per group) were treated with METH (1.25 mg/kg, given twice, 4 h apart) or vehicle (same schedule) at two different ambient temperatures (26 and 33°C). Core temperatures and plasma drug concentrations were measured during the period of drug exposure; striatal monoaminergic neuronal markers in the same monkeys were determined 1 week later. At the temperature range examined, the higher ambient temperature did not significantly enhance METH-induced hyperthermia or METH-induced dopaminergic neurotoxicity, although there were trends toward increases. Acute METH-induced increases in core temperature correlated highly and directly with subsequent decreases in striatal dopaminergic markers. Squirrel monkeys with the greatest increases in core temperature (and largest dopaminergic deficits) had the highest plasma drug metabolite (AMPH) concentrations. There was substantial interanimal variability, both with regard to elevations in core temperature and plasma drug concentrations. Pharmacokinetic studies in six additional squirrel monkeys revealed comparable individual differences in METH metabolism. These results, which provide the first available data on the within-subject relationship between temperature (ambient and core), plasma concentrations of METH (and AMPH), and subsequent dopaminergic neurotoxic changes, suggest that, as in rodents, core temperature can influence METH neurotoxicity in primates. In addition, they suggest that interanimal differences presently observed in thermal and neurotoxic responses to METH may be related to individual differences in drug metabolism.

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A single dose model of methamphetamine-induced neurotoxicity in rats: effects on neostriatal monoamines and glial fibrillary acidic protein

Cited by 100 publications

References 18 publications

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

Relationship between Temperature, Dopaminergic Neurotoxicity, and Plasma Drug Concentrations in Methamphetamine-Treated Squirrel Monkeys

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