Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes

Wagner, George C.; Lucot, James B.; Schuster, Charles R.; Seiden, Lewis S.

doi:10.1016/0006-8993(83)90602-9

Cited by 103 publications

(87 citation statements)

References 12 publications

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“…Moreover, it has been proposed that Meth toxicity is due to increased metabolism and free radical formation, enhanced by MAO inhibition (De Vito and Wagner 1989;Cadet et al 1994Cadet et al , 1997, leading to an increase in cytosolic DA pools (Marek et al 1990). In agreement, it has been reported that reserpine, but not a-methyl-p-tyrosine, enhances the longlasting DA depletion induced by Meth (Wagner et al 1983), and that Meth produces a redistribution from vesicular to cytosolic DA pools (Sulzer et al 1995;Frey et al 1997; Effect of methamphetamine on basal ganglia neurotransmission 651 Brown et al 2000). This results in an increase of cytosolic DA metabolism, which has been suggested to be neurotoxic via formation of free-radicals (see Sulzer and Zecca 2000), and/or o-semiquinone-radical species from aminochrome (Segura-Aguilar et al 2001).…”

Section: Discussionsupporting

confidence: 90%

Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

Bustamante

You²,

Castel

et al. 2002

Journal of Neurochemistry

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The main purpose of this study was to characterize the initial neurotransmission cascade elicited by methamphetamine, analysing simultaneously with in vivo microdialysis monoamine, amino acid and neuropeptide release in substantia nigra and neostriatum of the rat. The main effect of a single systemic dose of methamphetamine (15 mg/kg, subcutaneously) was an increase in dopamine levels, both in substantia nigra ( 10-fold) and neostriatum ( 40-fold), accompanied by a significant, but lesser, increase in dynorphin B ( two-fold, in both regions), and a decrease in monoamine metabolites. A similar effect was also observed after local administration of methamphetamine (100 lM) via the microdialysis probes, but restricted to the treated region. In other experiments, rats were repeatedly treated with methamphetamine or saline, with the last dose administered 12 h before microdialysis. Dopamine K + -stimulated release was decreased following repeated methamphetamine administration compared with that following saline, both in the substantia nigra (by 65%) and neostriatum (by 20%). In contrast, the effect of K + -depolarization on glutamate, aspartate and GABA levels was increased following repeated administration of methamphetamine. In conclusion, apart from an impairment of monoamine neurotransmission, repeated methamphetamine produces changes in amino acid homeostasis, probably leading to NMDA-receptor overstimulation.

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Section: Discussionsupporting

confidence: 90%

Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

Bustamante

You²,

Castel

et al. 2002

Journal of Neurochemistry

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“…6), suggesting that cell death in our model is not only dependent on enhanced cytosolic dopamine metabolism but on iron-mediated oxidative stress. These results are in agreement with previous studies showing that METH toxicity in mice can be blocked by the tyrosine hydroxylase inhibitor ␣-methyl-p-tyrosine (Wagner et al, 1983;Schmidt et al, 1985) by overexpression of superoxide dismutase (Cadet et al, 1994) or by pretreatment with antioxidants (Wagner et al, 1985;De Vito and Wagner, 1989). In this respect, our in vitro model bears great resemblance to in vivo models of METH toxicity.…”

Section: Discussionsupporting

confidence: 81%

Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

Lotharius

Falsig²,

Beek³

et al. 2005

J. Neurosci.

230

240

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Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies. For validation of putative neuroprotectants, a model is desirable in which the events leading to neurodegeneration replicate those occurring in the disease. We developed a human in vitro model of PD based on the assumption that dysregulated cytoplasmic dopamine levels trigger cell loss in this disorder. Differentiated human mesencephalic neuron-derived cells were exposed to methamphetamine (METH) to promote cytoplasmic dopamine accumulation. In the presence of elevated iron concentrations, as observed in PD, increased cytosolic dopamine led to oxidative stress, c-Jun N-terminal kinase (JNK) pathway activation, neurite degeneration, and eventually apoptosis. We examined the role of the mixed-lineage kinases (MLKs) in this complex degenerative cascade by using the potent inhibitor 3,9 -bis[(ethylthio)methyl]-K-252a (CEP1347). Inhibition of MLKs not only prevented FeCl2ϩ /METH-induced JNK activation and apoptosis but also early events such as neurite degeneration and oxidative stress. This broad neuroprotective action of CEP1347 was associated with increased expression of an oxidative stress-response modulator, activating transcription factor 4. As a functional consequence, transcription of the cystine/glutamate and glycine transporters, cellular cystine uptake and intracellular levels of the redox buffer glutathione were augmented. In conclusion, this new human model of parkinsonian neurodegeneration has the potential to yield new insights into neurorestorative therapeutics and suggests that enhancement of cytoprotective mechanisms, in addition to blockade of apoptosis, may be essential for disease modulation.

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“…Interestingly, both of these manipulations have been demonstrated previously to prevent the persistent DA deficits caused by METH treatment (Wagner et al, 1983;Schmidt et al, 1985;Axt et al, 1990;Bowyer et al, 1992;Bowyer et al, 1993;Albers and Sonsalla, 1995;Giovanni et al, 1995), presumably because both contribute to ROS or reactive nitrogen species formation (Cubells et al, 1994;Giovanni et al, 1995;Fleckenstein et al, 1997b;Yamamoto and Zhu, 1998; Figure 7. ␣MT pretreatment prevented the METH-induced higher molecular weight DAT complex formation ( A) although hyperthermia was maintained ( B).…”

Section: Discussionmentioning

confidence: 99%

“…This is significant because although DAT dimerization has been observed in cell lines (Hastrup et al, 2001; Sorkina et al, 2003;Torres et al, 2003) as well as in situ (Berger et al, 1994;Milner et al, 1994), it has not been reported in a native synaptosomal model without cross-linking reagents. The increase in DAT complex formation was attenuated by blocking both METH-induced hyperthermia and ␣MT pretreatment, regimens that prevent persistent METH-induced dopaminergic deficits (Wagner et al, 1983;Axt et al, 1990;Bowyer et al, 1992;Albers and Sonsalla, 1995). In contrast to the effects of multiple METH administrations, a single METH injection or multiple MDMA injections (regimens that do not lead to persistent dopaminergic deficits) had little effect on DAT complex formation.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Increases Dopamine Transporter Higher Molecular Weight Complex Formation via a Dopamine- and Hyperthermia-Associated Mechanism

Baucum¹,

Rau²,

Riddle³

et al. 2004

J. Neurosci.

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Multiple high-dose administrations of methamphetamine (METH) both rapidly (within hours) decrease plasmalemmal dopamine (DA) uptake and cause long-term deficits in DA transporter (DAT) levels and other dopaminergic parameters persisting weeks to months in rat striatum. In contrast, either a single administration of METH or multiple administrations of methylenedioxymethamphetamine (MDMA) cause less of an acute reduction in DA uptake and little or no persistent dopaminergic deficits. The long-term dopaminergic deficits caused by METH have been suggested, in part, to involve the DAT. Hence, this study assessed the impact of METH and MDMA administration on the DAT protein per se. Results revealed that multiple administrations of METH promoted formation of higher molecular weight (Ͼ170 kDa) DAT-associated protein complexes 24 -48 hr after treatment. This increase was attenuated by either preventing hyperthermia or pretreatment with the tyrosine hydroxylase inhibitor ␣-methyl-p-tyrosine; notably, each of these manipulations has also been demonstrated previously to prevent the persistent deficits in dopaminergic function caused by METH treatment. In contrast, either a single injection of METH or multiple injections of MDMA caused little or no formation of these DAT complexes. The addition of the reducing agent ␤-mercaptoethanol to samples prepared from METH-treated rats diminished the intensity of these complexes. Taken together, these data are the first to demonstrate higher molecular weight DAT complex formation in vivo and that such formation can be altered by both pharmacological and physiological manipulations. The implications of this phenomenon with regard to the neurotoxic potential of these stimulants are discussed.

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Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes

Cited by 103 publications

References 12 publications

Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

Progressive Degeneration of Human Mesencephalic Neuron-Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway

Methamphetamine Increases Dopamine Transporter Higher Molecular Weight Complex Formation via a Dopamine- and Hyperthermia-Associated Mechanism

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