Methamphetamine and MDMA (Ecstasy) Neurotoxicity: 'of Mice and Men'

Itzhak, Yossef; Achat-Mendes, Cindy

doi:10.1080/15216540410001727699

Cited by 53 publications

(43 citation statements)

References 42 publications

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“…Administration of METH (5 mg/kg Â 3) to Swiss Webster mice resulted in 42-61% depletion of DA and DAT in the striatum, frontal cortex and amygdala (Achat-Mendes et al, 2005;Itzhak and Achat-Mendes, 2004). In the present study, dopaminergic neurotoxicity was confirmed by the marked reduction of striatal TH-immunoreactive neurons and the significant increase in GFAP expression 5 days after METH administration to Swiss Webster mice (Figure 1).…”

Section: Discussionsupporting

confidence: 65%

“…We have previously shown that METH (5 mg/kg Â 3; 3 h apart) resulted in 42-61% depletion of DA-and DAT-binding sites in striatum, frontal cortex and amygdala of Swiss Webster mice (Achat-Mendes et al, 2005). Selective dopaminergic neurotoxicity with no evidence of serotonergic neurotoxicity (Itzhak and Achat-Mendes, 2004) was sustained for 95 days following METH administration to Swiss Webster mice (Itzhak et al, 2002). In the present study, METH-induced dopaminergic neurotoxicity was confirmed by immunohistochemical studies.…”

Section: Pretraining Dopaminergic Neurotoxicitymentioning

confidence: 99%

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Impairment in Consolidation of Learned Place Preference Following Dopaminergic Neurotoxicity in Mice is Ameliorated by N-acetylcysteine but not D1 and D2 Dopamine Receptor Agonists

Achat-Mendes

Anderson

Itzhak

2006

Neuropsychopharmacol

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Some of the major concerns related to methamphetamine (METH) abuse are the neuronal damage inflicted at dopamine (DA) nerve terminals and the cognitive deficits observed in human METH abusers. We have shown that a high dose of METH selectively depleted dopaminergic markers in striatum, frontal cortex and amygdala of Swiss Webster mice, and impaired learned place preference. In this study, we investigated whether deficits in consolidation of place learning, as a consequence of METH neurotoxicity, underlie the underperformance of cocaine conditioned place preference (CPP). Administration of METH (5 mg/kg Â 3) to Swiss Webster mice decreased striatal tyrosine hydroxylase (TH) immunoreactive neurons and significantly increased glial fibrillary acidic protein (GFAP) expression, confirming the neurotoxic potential of METH in mice. This treatment significantly attenuated the establishment of cocaine (15 mg/kg) CPP compared to control. To investigate whether manipulation of the consolidation phase improves learned place preference, mice were trained by cocaine and received daily post-training injections of DA receptor agonists or N-acetylcysteine (NAC). As memory consolidation occurs shortly after training, drugs were administered either immediately or 2 h post-training. Immediate posttraining administration of the D1 DA receptor agonist SKF38393 (5, 10, and 20 mg/kg) or the D2 DA receptor agonist quinpirole (0.25, 0.5, and 1.0 mg/kg) did not improve the establishment of CPP following METH neurotoxicity. However, immediate but not delayed NAC administration (50 and 100 mg/kg) enhanced cocaine CPP following METH neurotoxicity and had no effect on control CPP. The levels of the reduced form of glutathione (GSH) in striatum, amygdala, hippocampus and frontal cortex were significantly lower in METH-treated mice compared to control during the period of CPP training. Acute and repeated administration of NAC to METH-treated mice restored the decreased brain GSH but had no effect on controls. Results suggest that METH-induced dopaminergic neurotoxicity is associated with impairment of consolidation of learned place preference, and that this impairment is improved by immediate posttraining administration of the glutathione precursor NAC and not by D1 or D2 DA receptor agonists. Restoration of brain glutathione levels immediately post-training may facilitate the consolidation process.

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Section: Discussionsupporting

confidence: 65%

Section: Pretraining Dopaminergic Neurotoxicitymentioning

confidence: 99%

Impairment in Consolidation of Learned Place Preference Following Dopaminergic Neurotoxicity in Mice is Ameliorated by N-acetylcysteine but not D1 and D2 Dopamine Receptor Agonists

Achat-Mendes

Anderson

Itzhak

2006

Neuropsychopharmacol

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“…Results from studies in humans, non-human primates and rodents support the view that these compounds cause structural damage to monoamine nerve terminals and are thereby neurotoxic (O'Callaghan, 2002a, Lyles and Cadet, 2003, Itzhak and Achat-Mendes, 2004. Such data include the finding that repeated high-dose administration of METH results in a reduction in striatal dopamine (DA) and serotonin (5-HT) concentrations (Kogan et al, 1976, Wagner et al, 1980, a decrease in the activity of tyrosine and tryptophan hydroxylase, the rate-limiting enzymes responsible for the production of DA and 5-HT (Hotchkiss and Gibb, 1980), and reduced number of amine uptake sites (Wagner et al, 1980).…”

supporting

confidence: 56%

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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“…Importantly, in the mouse, MDMA is much more of a dopaminergic agent than it appears to be in other species, eliciting neurochemical and behavioral effects similar to those of METH after both acute and chronic treatment (O'Callaghan and Miller, 1994;Mann et al, 1997;Itzhak and Achat-Mendes, 2004;Fantegrossi et al, 2008;Panas et al, 2010;Granado et al, 2011;Murnane et al, 2012). These observed similarities between the effects of MDMA and METH are likely because of similar neuropharmacology of these compounds in the mouse.…”

Section: Introductionmentioning

confidence: 63%

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

Fantegrossi

Gannon

Zimmerman

et al. 2012

Neuropsychopharmacol

138

151

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In recent years, synthetic analogues of naturally occurring cathinone have emerged as psychostimulant-like drugs of abuse in commercial 'bath salt' preparations. 3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of these illicit products, and its structural similarities to the more well-known drugs of abuse 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) suggest that it may have similar in vivo effects to these substances. In these studies, adult male NIH Swiss mice were trained to discriminate 0.3 mg/kg MDPV from saline, and the interoceptive effects of a range of substitution doses of MDPV, MDMA, and METH were then assessed. In separate groups of mice, surgically implanted radiotelemetry probes simultaneously monitored thermoregulatory and locomotor responses to various doses of MDPV and MDMA, as a function of ambient temperature. We found that mice reliably discriminated the MDPV training dose from saline and that cumulative doses of MDPV, MDMA, and METH fully substituted for the MDPV training stimulus. All three drugs had similar ED 50 values in this procedure. Stimulation of motor activity was observed following administration of a wide range of MDPV doses (1-30 mg/kg), and the warm ambient temperature potentiated motor activity and elicited profound stereotypy and self-injurious behavior at 30 mg/kg. In contrast, MDPV-induced hyperthermic effects were observed in only the warm ambient environment. This pattern of effects is in sharp contrast to MDMA, where ambient temperature interacts with thermoregulation, but not locomotor activity. These studies suggest that although the interoceptive effects of MDPV are similar to those of MDMA and METH, direct effects on thermoregulatory processes and locomotor activity are likely mediated by different mechanisms than those of MDMA.

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Methamphetamine and MDMA (Ecstasy) Neurotoxicity: 'of Mice and Men'

Cited by 53 publications

References 42 publications

Impairment in Consolidation of Learned Place Preference Following Dopaminergic Neurotoxicity in Mice is Ameliorated by N-acetylcysteine but not D1 and D2 Dopamine Receptor Agonists

Impairment in Consolidation of Learned Place Preference Following Dopaminergic Neurotoxicity in Mice is Ameliorated by N-acetylcysteine but not D1 and D2 Dopamine Receptor Agonists

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

In vivo Effects of Abused ‘Bath Salt’ Constituent 3,4-methylenedioxypyrovalerone (MDPV) in Mice: Drug Discrimination, Thermoregulation, and Locomotor Activity

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