The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice

Zhu, Jimmy; Xu, Wenjing; Wang, Jing; Ali, Syed F.; Angulo, Jesús A.

doi:10.1111/j.1471-4159.2009.06330.x

Cited by 26 publications

(31 citation statements)

References 58 publications

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“…Clearly, studies with strict control over potential contributing factors allowing for systematic independent and coordinate manipulation of the factors will be necessary to fully understand the process by which METH induces DA neurotoxicity. Furthermore, we cannot exclude a role of NO in striatal-efferent neuron toxicity observed in some models of METH-induced neurotoxicity (Zhu et al, 2009). Although the necessity of NO for METH-induced DA neurotoxicity remains in question, it is clear from the present findings that administration of a binge regimen of METH increases NO production.…”

Section: Discussionmentioning

confidence: 96%

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

Friend

Son

Keefe

et al. 2012

J Pharmacol Exp Ther

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Nitric oxide is implicated in methamphetamine (METH)-induced neurotoxicity; however, the source of the nitric oxide has not been identified. Previous work has also revealed that animals with partial dopamine loss induced by a neurotoxic regimen of methamphetamine fail to exhibit further decreases in striatal dopamine when re-exposed to methamphetamine 7-30 days later. The current study examined nitric oxide synthase expression and activity and protein nitration in striata of animals administered saline or neurotoxic regimens of methamphetamine at postnatal days 60 and/or 90, resulting in four treatment groups: Saline:Saline, METH:Saline, Saline:METH, and METH: METH. Acute administration of methamphetamine on postnatal day 90 (Saline:METH and METH:METH) increased nitric oxide production, as evidenced by increased protein nitration. Methamphetamine did not, however, change the expression of endothelial or inducible isoforms of nitric oxide synthase, nor did it change the number of cells positive for neuronal nitric oxide synthase mRNA expression or the amount of neuronal nitric oxide synthase mRNA per cell. However, nitric oxide synthase activity in striatal interneurons was increased in the Saline: METH and METH:METH animals. These data suggest that increased nitric oxide production after a neurotoxic regimen of methamphetamine results from increased nitric oxide synthase activity, rather than an induction of mRNA, and that constitutively expressed neuronal nitric oxide synthase is the most likely source of nitric oxide after methamphetamine administration. Of interest, animals rendered resistant to further methamphetamine-induced dopamine depletions still show equivalent degrees of methamphetamine-induced nitric oxide production, suggesting that nitric oxide production alone in response to methamphetamine is not sufficient to induce acute neurotoxic injury.

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Section: Discussionmentioning

confidence: 96%

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

Friend

Son

Keefe

et al. 2012

J Pharmacol Exp Ther

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“…The excessively high levels of extracellular dopamine induced by METH initiate a neurotoxic cascade producing free radicals and quinones that are damaging to proteins (Fornstedt and Carlsson, 1989; Hastings et al, 1996). The protracted overflow of dopamine induced by METH promotes the overflow of the excitotoxic transmitter glutamate (Nash and Yamamoto, 1992), nitric oxide production (Taraska and Finnegan, 1997; Zhu et al, 2009), microglial activation (LaVoie et al, 2004; Thomas et al, 2004), and bioenergetic compromise due to mitochondrial dysfunction (Chan et al, 1994; Brown and Yamamoto, 2003). The neurotoxic state induced by METH causes pre-synaptic neural damage including reduction of dopamine transporter function (Fleckenstein et al, 1997), oligomerization of the transporter (Baucum et al, 2004), decreased vesicular transporter function (Fleckenstein et al, 2003), inhibition of tyrosine hydroxylase activity (Hotchkiss et al, 1979), and protein levels (Yu et al, 2004), decreased tissue dopamine content (Wagner et al, 1980) and degeneration of striatal dopamine terminals (Ricaurte et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

“…Evidence implicating nitric oxide production in the striatal METH-induced neural damage accrues from pharmacological studies demonstrating that antagonists of neuronal nitric oxide synthase protect the striatum from METH (Itzhak and Ali, 1996; Itzhak et al, 2000), moreover, mice lacking the neuronal nitric oxide synthase gene show partial resistance to METH (Imam et al, 2001). Our laboratory has shown that the METH-induced elevation of striatal 3-nitrotyrosine (an indirect index of nitric oxide production) was significantly attenuated by pretreatment with a neurokinin-1 receptor antagonist (Zhu et al, 2009). The striatal neurokinin-1 receptors are expressed by cholinergic and somatostatin/NPY/NOS interneurons.…”

Section: Introductionmentioning

confidence: 99%

“…The latter population is comprised of approximately 1% of striatal neurons and is the only striatal neuron expressing the neuronal nitric oxide synthase (Kawaguchi et al, 1995). Interestingly, ablation of the striatal somatostatin/NPY/NOS interneurons with the selective neurotoxin substance P-saporin completely abrogated the METH-induced apoptosis of some striatal neurons (Zhu et al, 2009). Evidence implicating the neurokinin-1 receptor and nitric oxide production comes from studies involving cultured synoviocytes that respond to substance P (natural ligand of the neurokinin-1 receptor) by augmenting nitric oxide production (O’Shaughnessy et al, 2006) and also in rat skin microvasculature (Ralevic et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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Synergism between methamphetamine and the neuropeptide substance P on the production of nitric oxide in the striatum of mice

Wang

Angulo

2011

Brain Research

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Our laboratory has been investigating the participation of striatal neurokinin-1 receptors in the methamphetamine (METH)-induced loss of striatal neurons. Signaling through these receptors exacerbates the METH-induced striatal apoptosis. METH induces the synthesis of nitric oxide (NO) and the latter has been linked to the activation of neurodegenerative cascades. In the present study, we assessed the role of the neurokinin-1 receptor in the production of striatal 3-nitrotyrosine (3-NT) and L-citrulline (indirect indices of NO production). To that end, we injected male mice with a bolus of METH (30 mg/kg, ip) and visualized striatal neuronal nitric oxide synthase (NOS)-positive cells by immunohistochemistry and protein levels by Western blot. The expression of neuronal NOS or protein levels at 2, 4 & 8 hours post-METH was unchanged. Next, we assessed 3-NT and L-citrulline by immunohistochemistry. At 4 hours post-METH, striatal 3-NT and Lcitrulline levels were increased 30-and 5-fold, respectively, relative to controls and the selective neurokinin-1 receptor antagonist WIN-51,708 attenuated these increases. Intrastriatal infusion of the neurokinin-1 receptor agonist GR-73632 induced striatal 3-NT production that was attenuated with systemic injection of WIN-51,708 or 7-nitroindazole (7-NI, an inhibitor of neuronal NOS). Moreover, infusion of calmidazolium (calmodulin inhibitor) with GR-73632 prevented the production of 3-NT. These data are consistent the hypothesis that METH-induced production of NO is modulated by the striatal neurokinin-1 receptors and that this receptor may participate in the biochemical activation of neuronal NOS.

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“…In recent years it has been demonstrated that apart from classical monoaminergic toxicity, METH induces non-monoaminergic neuronal soma degeneration in the striatum of rodents (Jayanthi et al, 2004(Jayanthi et al, , 2005Zhu et al, 2009). The affected cells have been identified as the GABAergic neurons expressing enkephalin and parvalbumin (Jayanthi et al, 2005;Thiriet et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The JNK inhibitor, SP600125, potentiates the glial response and cell death induced by methamphetamine in the mouse striatum

Urrutia

Granado

Gutiérrez-López

et al. 2013

Int. J. Neuropsychopharm.

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This study investigates the effect of the selective Jun NH2-terminal kinase 1/2 (JNK1/2) inhibitor, (SP600125) on the striatal dopamine nerve terminal loss and on the increased interleukin-15 (IL-15) expression and glial response induced by methamphetamine (METH). Mice were given repeated low doses of METH (4 mg/kg, i.p., three times separated by 3 h) and killed 24 h or 7 d after the last dose. SP600125 (30 mg/kg, i.p) was administered 30 min before the last METH injection. Results indicate that METH produced dopaminergic axonal neurotoxicity reflected as a marked decrease in the striatal density of tyrosine hydroxylase-immunoreactive (TH-ir) fibres and dopamine transporter-immunoreactivity (DAT-ir) 24 h after dosing. These effects were not modified by SP600125. This compound also failed to prevent the long-term loss of dopamine levels and DAT observed 7 d following METH injection. Nevertheless, SP600125 potentiated METH-induced striatal cell loss reflected by an increase in Fluoro-Jade immunostaining, cleaved capase-3 immunoreactivity and the number of terminal deoxyncleotidyl transferase-mediated dUTP nick end labelling (TUNEL) positive cells. In line with a deleterious effect of JNK1/2 inhibition, SP600125 increased the astroglial and microglial response induced by METH and interfered with drug-induced IL-15 expression. Together these data indicate that, not only does SP600125 fail to protect against the dopaminergic damage induced by METH but also, in fact, it potentiates the glial response and the non-dopaminergic striatal cell loss caused by the drug.

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The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice

Cited by 26 publications

References 58 publications

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

Expression and Activity of Nitric Oxide Synthase Isoforms in Methamphetamine-Induced Striatal Dopamine Toxicity

Synergism between methamphetamine and the neuropeptide substance P on the production of nitric oxide in the striatum of mice

The JNK inhibitor, SP600125, potentiates the glial response and cell death induced by methamphetamine in the mouse striatum

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