Low Environmental Temperatures or Pharmacologic Agents That Produce Hypothermia Decrease Methamphetamine Neurotoxicity in Mice

Ali, Syed F.; Newport, Glenn D.; Holson, R.Robert; Slikker, William; Bowyer, John F.

doi:10.1111/j.1749-6632.1995.tb16610.x

Cited by 60 publications

(93 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, as mentioned above, in situ hybridization studies indicate that although the increase in COX1 expression takes place in the substantia nigra, it occurs in the pars reticulata, in a region where GABA, rather than DA, cell bodies are located (González-Hernández and Rodríguez, 2000). Nevertheless, when we tested the effects of METH given at low ambient temperature, which induces hypothermia and prevents METH-induced DA neurotoxicity (Ali et al, 1995;Xie et al, 2000), no increase in COX1 expression was observed, further attesting to the close link between METHinduced DA neurotoxicity and increased COX1 expression. Clearly, to completely delineate the role of COX1 in METH neurotoxicity, additional studies will be necessary.…”

Section: Discussionmentioning

confidence: 84%

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

Xie¹,

Tong²,

Barrett

et al. 2002

J. Neurosci.

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionmentioning

confidence: 84%

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

Xie¹,

Tong²,

Barrett

et al. 2002

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Membranes were assayed in triplicate using a 1.0 nM concentration of [ 3 H]citalopram (84.2 Ci/ mmol, New England Nuclear) with 10 mM unlabeled fluoxetine to determine nonspecific binding. For the 1-week cohort, samples of cortex and hippocampus collected from the other cerebral hemisphere were analyzed for 5-HT and 5-HIAA concentrations by high-performance liquid chromatography with electrochemical detection (Ali et al, 1994).…”

Section: Neurochemical Measures (7 or 67 Days)mentioning

confidence: 99%

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

Piper

Fraiman

Owens

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, SpragueDawley rats (N ¼ 67) received MDMA (4 Â 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems.

show abstract

“…The tissues were sonicated in ice-cold 0.2 M HClO 4 (20% W/V) that contained 100 ng/ml of an internal standard (3,4-dihydroxybenzylamine). After separation by a brief centrifugation, 150 μl of the supernatant was passed through a 0.2 μm Nylon-66 filter and 25 μl of the filtrate was injected on to a HPLC column coupled to an electrochemical detector as previously described (Ali et al, 1994;Zhang et al, 2004). The concentrations of DA, DOPAC, and HVA were calculated using a three-point standard curve generated by determining the known amounts of internal standards.…”

Section: Determination Of Biogenic Amine Levelsmentioning

confidence: 99%

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

et al. 2007

View full text Add to dashboard Cite

Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine. There is a resultant hyperphenylalanemia with subsequent impairment in cognitive abilities, executive functions and motor coordination. The neuropathogenesis of the disease has not been completely elucidated, however, oxidative stress is considered to be a key feature of the disease process. Hyperphenylalanemia also adversely affects monoaminergic metabolism in the brain. For this reason we chose to evaluate the nigrostriatum of Pah enu2 mice, to determine if alterations of monoamine metabolism resulted in morphologic nigrostriatal pathology. Furthermore, we believe that recent developments in adeno-associated virus (AAV)-based vectors have greatly increased the potential for long-term gene therapy and may be a viable alternative to dietary treatment for this metabolic disorder. In this study we identified neurodegenerative changes with regenerative responses in the nigrostriatum of Pah enu2 mice that are consistent with oxidative injury and occurred as early as 4 weeks of age. These neuropathologic changes were reversed following portal vein delivery of a recombinant adeno-associated virus-mouse phenylalanine hydroxylase-woodchuck hepatitis virus post-transcriptional response element (rAAV-mPAH-WPRE) vector to Pah enu2 mice and corresponded to rapid reduction of serum Phe levels.

show abstract

Low Environmental Temperatures or Pharmacologic Agents That Produce Hypothermia Decrease Methamphetamine Neurotoxicity in Mice

Cited by 60 publications

References 0 publications

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

Dissociation of the Neurochemical and Behavioral Toxicology of MDMA (‘Ecstasy’) by Citalopram

PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pahenu2 mice

Contact Info

Product

Resources

About