Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain

Ricaurte, George A.; Güillery, R. W.; Seiden, Lewis S.; Schuster, Charles R.; Moore, Robert Y.

doi:10.1016/0006-8993(82)90198-6

Cited by 446 publications

(271 citation statements)

References 22 publications

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“…In contrast to previously published observations using the acute toxic dosing model (i.e., four injections of METH every 2 h; Daberkow et al, 2005;Eyerman and Yamamoto, 2005;Friedman et al, 1998;Ricaurte et al 1982;Straiko et al, 2007;Wallace et al, 2001), METH administration to rats not exposed to CUS did not produce depletions in 5-HT tissue content (Fig. 3B).…”

Section: Discussioncontrasting

confidence: 99%

“…The neurotoxic effects are evidenced by long-term depletions in striatal dopamine (DA) and serotonin (5-HT) concentrations, and their uptake sites (Friedman et al, 1998;Ricaurte et al, 1982;Wagner et al, 1980), decreases in tryptophan and tyrosine hydroxylase activity (Bakhit et al, 1981), and cell loss (Deng et al, 2007;Sonsalla et al, 1996;Thiriet et al, 2005;Yu et al, 2004;Zhu et al, 2006). In addition to the hypotheses of oxidative stress and apoptosis as mechanisms of METH-induced neurotoxicity (for review, see Davidson et al, 2001;Kita et al, 2003;Quinton and Yamamoto, 2006), increases in the extracellular concentrations of glutamate (GLU) have been also suggested to play an important role (Abekawa et al, 1994;Nash and Yamamoto, 1992;Sonsalla et al, 1989;Stephans and Yamamoto, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Tata

Yamamoto

2008

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Striking parallels exist between the neurochemical and toxic effects of stress and methamphetamine. Despite these similarities, no studies have examined how stress may promote the toxic effects of methamphetamine (METH). The current study tested the hypothesis that chronic stress enhances METH toxicity by augmenting glutamate (GLU) release and excitotoxicity in response to METH administration. Adult male Sprague-Dawley rats were exposed to 10 days of unpredictable stress and then received either saline or METH (7.5 mg/kg, i.p., once every 2 h × four injections). Prior exposure to unpredictable stress acutely enhanced the striatal extracellular GLU concentrations in response to METH, and eventually caused proteolysis of the cytoskeleton protein spectrin. Administration of the corticosterone synthesis inhibitor, metyrapone (25 mg/kg, i.p., prior to each stressor), during unpredictable stress attenuated the enhanced striatal GLU release in response to METH, blocked spectrin proteolysis, and attenuated METH-associated toxicity measured by long-term depletions in the dopamine and serotonin tissue content as well as depletions in dopamine and serotonin transporter immunoreactivity of the striatum. In summary, prior exposure to unpredictable stress enhances METH-induced elevations of GLU in the striatum, resulting in long-term excitotoxic damage and an augmentation of damage to dopamine and serotonin terminals. These studies provide a neurochemical basis for how stress contributes to the deleterious effects of METH abuse.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Tata

Yamamoto

2008

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“…In sufficient doses, mAMPH causes long-term damage to DA terminals in the striatum and to forebrain 5-HT terminals, as evidence by long-term depletions in these two neurotransmitters, their synthetic enzymes, metabolites, and plasma membrane transporters (Koda and Gibb, 1973;Hotchkiss and Gibb, 1980;Schmidt et al, 1985;Wagner et al, 1979;Ricaurte et al, 1982;Axt and Molliver, 1991;Friedman et al, 1998;Chapman et al, 2001). The mAMPH-induced depletions of DA reverse with a very slow time course (Cass and Manning, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, this regimen causes degeneration of neurons in somatosensory cortex (Commins and Seiden, 1986;O'Dell and Marshall, 2000). The dopaminergic loss has been interpreted as neurotoxicity on the basis of both neurochemical and histological evidence (Koda and Gibb, 1973;Fibiger and McGeer, 1971;Seiden et al, 1975;Ricaurte et al, 1982;Volkow et al, 2001a, b;McCann et al, 1998), but the issue of whether mAMPH induces DA terminal degeneration has been challenged by studies of mAMPH-treated animals (Harvey et al, 2000) and human mAMPH abusers (Wilson et al, 1996;Volkow et al, 2001a, b). Whether or not the decreases in markers of DA and 5-HT terminals constitute terminal degeneration or a long-lasting phenotypic downregulation, the focus of the present study was to determine the cognitive consequences of this loss of monoaminergic markers.…”

Section: Discussionmentioning

confidence: 99%

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

Belcher

O’Dell

Marshall

2005

Neuropsychopharmacol

106

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Repeated moderate doses of methamphetamine (mAMPH) damage forebrain monoaminergic terminals and nonmonoaminergic cells in somatosensory cortex, and impair performance in a novelty preference task of object recognition (OR). This study aimed to determine whether the memory deficit seen after a neurotoxic mAMPH regimen results from damage to dopamine (DA) and/or serotonin (5-HT) terminals. Animals were given a neurotoxic regimen of mAMPH, p-chloroamphetamine (PCA, preferentially damages 5-HT terminals), damphetamine (d-AMPH, preferentially damages DA terminals), or saline. After 1 week, animals were trained and tested for OR memory. Rats treated with mAMPH showed no recognition memory during the short-term memory (STM) test, whereas both PCA-and d-AMPH-treated rats showed OR STM scores comparable to controls. After behavioral testing, the specificity of monoaminergic lesions was determined by postmortem [ 125 I]RTI-55 binding to dopamine (DAT) and serotonin (SERT) transporter proteins. Tissue from a separate group of animals killed 3 days after drug treatment was processed for Fluoro-Jade (F-J) fluorescence histochemistry to detect damaged cortical neurons. mAMPH-treated rats showed reductions in striatal DAT and hippocampal (HC) and perirhinal (pRh) SERT, as well as degeneration of neurons in primary somatosensory cortex. In PCA-treated rats, HC and pRh SERT were substantially depleted, but striatal DAT and cortical neuron survival were unaffected. By contrast, d-AMPH-treated animals showed marked depletions in striatal DAT and cortical neurodegeneration, but HC and pRh SERT were unaffected. This pattern of results indicates that no single feature of mAMPH-induced neurotoxicity is sufficient to produce the OR impairments seen after mAMPH treatment.

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“…Evidence from animal and human studies suggests that long-term exposure or high dosages of amphetamines causes neuronal damage. Anatomical evidence supporting the neurotoxic potential of METH stems from studies showing that a high dose of METH given to rats caused degeneration of dopamine (DA) nerve terminals, and loss of tyrosine hydroxylase (TH), DA transporter (DAT), tryptophan hydroxylase (TPH), and 5-hydroxytryptamine (5-HT) axon terminals (Axt and Molliver, 1991;Gibb et al, 1990;Ricaurte et al, 1982;Seiden and Sabol, 1996). Further support for the neurotoxic potential of METH comes from evidence that (a) high doses of METH cause striatal gliosis as shown by an increase of glial fibrillary acidic protein (GFAP) in rats and mice (Battaglia et al, 2002;O'Callaghan and Miller, 1994;Sheng et al, 1994), and (b) apoptotic pathways are involved in METH-induced neuronal injury .…”

Section: Introductionmentioning

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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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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Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain

Cited by 446 publications

References 22 publications

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Chronic stress enhances methamphetamine‐induced extracellular glutamate and excitotoxicity in the rat striatum

Impaired Object Recognition Memory Following Methamphetamine, but not p-Chloroamphetamine- or d-Amphetamine-Induced Neurotoxicity

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

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