Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity

O’Dell, Steven J.; Weihmuller, Fredric B.; Marshall, John F.

doi:10.1016/0006-8993(91)91461-9

Cited by 178 publications

(127 citation statements)

References 26 publications

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“…As shown in Tables 3 and 4, K + -depolarization in neostriatum produced a significant increase of striatal, but also of nigral Dyn B levels, indicating a monosynaptic interaction. While the effect of high doses of Meth on DA release has been extensively demonstrated (O'Dell et al 1991;Kuczenski and Segal 1992;Nash and Yamamoto 1992;Abekawa et al 1994), this is the first time that the effect of Meth on monoamines, amino acids and neuropeptides is simultaneously analysed in substantia nigra and neostriatum, which is relevant, as the neurotoxic effect of Meth has been observed in terminals, but not in cell body regions (Brunswick et al 1992).…”

Section: Discussionmentioning

confidence: 93%

“…Furthermore, while, as measured by quantitative autoradiography, the neurotoxic effect of Meth is seen in widespread brain regions receiving monoamine terminals, the cell body regions are largely unaffected (Brunswick et al 1992). It has been proposed that the long-term effects of Meth depend on the amount of overflow of DA induced by the drug (O'Dell et al 1991), and, in agreement, it has been shown that Meth-induced damage is prevented by inhibition of DA synthesis (Gibb and Kogan 1979;Hotchkiss and Gibb 1980;, DA transport Marek et al 1990), or even by DA receptor antagonism (Sonsalla et al 1986;O'Dell et al 1993). It has been argued, however, that Meth may also increase glutamate (Glu) overflow (Sonsalla et al 1989;Nash and Yamamoto 1992;Stephans and Yamamoto 1994), leading to the hypothesis that there is a synergism between both DA and Glu release, and that this is a requirement for Meth-induced neurotoxicity (Abekawa et al 1994;Eisch et al 1996).…”

mentioning

confidence: 99%

“…Microdialysis has been proposed as a method for monitoring in vivo neurotransmitter release, in brain and peripheral tissue (Ungerstedt et al 1982;see Ungerstedt 1984see Ungerstedt , 1991, and it has been widely used for monitoring the effects of amphetamines (Zetterström et al 1983(Zetterström et al , 1986Westerink et al 1987;Butcher et al 1988;Hurd and Ungerstedt 1989a,b), including those of Meth (O'Dell et al 1991;Nash and Yamamoto 1992;Holson et al 1996;Sabol et al 2001).…”

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confidence: 99%

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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: Discussionmentioning

confidence: 93%

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confidence: 99%

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confidence: 99%

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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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“…Regardless of the intake patterns, the long-access animals in the current study achieved very high levels of methamphetamine exposure. Indeed, the cumulative dose amounts over the 14-day maintenance period in the long-access group (>90 mg/kg) surpassed doses administered in non-contingent "binge" paradigms, which typically employ acute injections in a single day (ranging from one to four single doses of 1 to 10 mg/kg) that produce cumulative totals of 4 to 40 mg/kg (Itzhak et al 2002;O'Dell et al 1991;Zhu et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

2008

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Rationale-Methamphetamine is a highly addictive psychostimulant, and chronic methamphetamine users show high rates of relapse. Furthermore, prolonged methamphetamine abuse can lead to psychiatric symptoms and has been associated with various cognitive dysfunctions. However, the impact of self-administered methamphetamine on cognitive dysfunction and relapse has not been concurrently examined in an animal model.Objectives-The present study determined the effects of short-vs. long-access contingent methamphetamine on self-administration, extinction responding, reinstatement of methamphetamine seeking, and cognitive performance on an object exploration task.Materials and methods-Long-Evans rats self-administered methamphetamine i.v. (0.02 mg/ infusion) or received saline during daily sessions (1 or 2 h) for 10 days, followed by either maintained short-(1 or 2 h) or long-access (6 h) self-administration for 14 days. Lever responding was extinguished prior to reinstatement, which consisted of presentation of drug-paired cues or a priming injection of methamphetamine (1.0 mg/kg). Animals were also tested on an object exploration task prior to self-administration and at 10−12 days after cessation of self-administration, thus providing a comparison of pre-methamphetamine exposure with post-methamphetamine exposure.Results-Long-access methamphetamine self-administration resulted in escalation of daily intake. Furthermore, animals in both short-and long-access groups showed robust conditioned-cued and drug-primed reinstatement, with long access resulting in enhanced methamphetamine-primed reinstatement. Methamphetamine self-administration also led to access-dependent impairments on novel object recognition but failed to impair recognition of spatial reconfiguration.Conclusions-Extended methamphetamine self-administration enhances drug-primed reinstatement and decreases novel object recognition, indicating that prolonged contingent methamphetamine increases motivation for drug seeking following withdrawal while increasing cognitive deficits.

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“…This was done recognizing that when using W I N35,428, one is blocking not only M ETH-induced DA neurotoxicity but also M ETH-induced DA release (and all of the postsynaptic actions of DA), which may or may not be associated with the neurotoxic process. Although this approach has the potential to identif y or include candidate genes that, although perhaps related to DA release, are not directly liked to M ETH-induced DA neurotoxicity, there is evidence that M ETH-induced DA release is linked to M ETH-induced DA neurotoxicity (O'Dell et al, 1991). For microarray studies, ventral midbrain tissues (n ϭ 12 per group) were collected 3, 6, 12, and 24 hr after treatment with M ETH (45 mg / kg, s.c.), W I N35,428 (12.5 mg / kg, i.p., immediately before M ETH) plus M ETH, W I N35,428 alone, or saline.…”

Section: Drugsmentioning

confidence: 99%

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

Xie¹,

Tong²,

Barrett

et al. 2002

J. Neurosci.

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The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstreamregulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated. Key words: amphetamines; neurotoxicity; dopamine; neurodegeneration; cytochrome c oxidase; microarrayDespite considerable investigation (Gibb et al., 1994;Lew et al., 1997), the mechanisms underlying the neurotoxic effects of methamphetamine (METH) on brain dopamine (DA) neurons remain unknown. However, a considerable body of data attests to the importance of DA transporter (DAT) function and temperature. The essential role of the DAT in METH-induced DA neurotoxicity has been demonstrated by the observation that DAT inhibitors afford complete neuroprotection (Ricaurte et al., 1984; Marek et al., 1990a,b;Pu et al., 1994) and the finding that DAT knock-out mice are insensitive to METH neurotoxicity (Fumagalli et al., 1998). The importance of temperature has been documented by studies demonstrating that decreases in core temperature protect against METH neurotoxicity, whereas increases in core temperature exacerbate the toxicity (Bowyer et al., 1994;Miller and O'Callaghan, 1994;Albers and Sonsalla, 1995;Ali et al., 1996). Furthermore, there is evidence that at least part of the effect of temperature on METH neurotoxicity is mediated at the level of the DAT (Xie et al., 2000). More recent studies have also i...

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Multiple methamphetamine injections induce marked increases in extracellular striatal dopamine which correlate with subsequent neurotoxicity

Cited by 178 publications

References 26 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

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

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