Subchronic apocynin treatment attenuates methamphetamine-induced dopamine release and hyperactivity in rats

Miller, Dennis K.; Oelrichs, Clark E.; Sun, Grace Y.; Simonyi, Ágnes

doi:10.1016/j.lfs.2013.12.031

Cited by 19 publications

(13 citation statements)

References 29 publications

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“…The last dose of apocynin was given 30 min before MA injection (Additional file 2 : Fig S5). The dose of apocynin was determined based on a previous study [ 49 ]. U0126 (ERK inhibitor; Tocris Bioscience, Ellisville, MO, USA) was dissolved in DMSO as a stock solution and then stored at −20 °C.…”

Section: Methodsmentioning

confidence: 99%

“…Importantly, a recent investigation demonstrated that treatment with apocynin, a non-specific inhibitor of PHOX [ 48 ], results in a significant reduction in MA-induced dopamine-release from rat striatal slices [ 49 ]. Furthermore, Park et al [ 50 ] found that MA (10 μM) induces an increase in phosphorylation of the p47phox subunit and subsequently enhanced PHOX activity in endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK

Dang

Shin

Nam

et al. 2016

J Neuroinflammation

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BackgroundActivation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice.MethodsWe examined changes in mitogen-activated protein kinases (MAPKs), mitochondrial function [i.e., mitochondrial membrane potential, intramitochondrial Ca2+ accumulation, mitochondrial oxidative burdens, mitochondrial superoxide dismutase expression, and mitochondrial translocation of the cleaved form of protein kinase C delta type (cleaved PKCδ)], microglial activity, and pro-apoptotic changes [i.e., cytosolic cytochrome c release, cleaved caspase 3, and terminal deoxynucleotidyl transferase dUDP nick-end labeling (TUNEL) positive populations] after a neurotoxic dose of MA in the striatum of mice to achieve a better understanding of the effects of apocynin, a non-specific PHOX inhibitor, or genetic inhibition of p47phox (by using p47phox knockout mice or p47phox antisense oligonucleotide) against MA-induced dopaminergic neurotoxicity.ResultsPhosphorylation of extracellular signal-regulated kinases (ERK1/2) was most pronounced out of MAPKs after MA. We observed MA-induced phosphorylation and membrane translocation of p47phox in the striatum of mice. The activation of p47phox promoted mitochondrial stresses followed by microglial activation into the M1 phenotype, and pro-apoptotic changes, and led to dopaminergic impairments. ERK activated these signaling pathways. Apocynin or genetic inhibition of p47phox significantly protected these signaling processes induced by MA. ERK inhibitor U0126 did not exhibit any additional positive effects against protective activity mediated by apocynin or p47phox genetic inhibition, suggesting that ERK regulates p47phox activation, and ERK constitutes the crucial target for apocynin-mediated inhibition of PHOX activation.ConclusionsOur results indicate that the neuroprotective mechanism of apocynin against MA insult is via preventing mitochondrial burdens, microglial activation, and pro-apoptotic signaling process by the ERK-dependent activation of p47phox.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0478-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK

Dang

Shin

Nam

et al. 2016

J Neuroinflammation

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“…The reinforcing properties of METH are mediated by an elevation of extracellular DA levels in the dorsal and ventral striatum through METH’s interaction with the DA transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) (Volkow et al, 2007). For example, exposure to METH or amphetamine increases locomotor activity by increasing extracellular DA release in the dorsal and ventral striatum (Frankel et al, 2007; Kuczenski et al, 1991; Miller et al, 2014). In addition, repeated exposure to METH can cause neurotoxicity via formation of reactive oxygen species (ROS) in DAergic neurons (Sun et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens

et al. 2016

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Methamphetamine (METH) markedly increases dopamine (DA) release in the mesolimbic DA system, which plays an important role in mediating the reinforcing effects of METH. Methamphetamine-induced DA release results in the formation of reactive oxygen species (ROS), leading to oxidative damage. We have recently reported that ROS are implicated in behavior changes and DA release in the nucleus accumbens (NAc) following cocaine administration. The aim of this study was to evaluate the involvement of ROS in METH-induced locomotor activity, self-administration, and enhancement of DA release in the NAc. Systemic administration of a non-specific ROS scavenger, N-tert-butyl-α-phenylnitrone (PBN; 0, 50 and 75 mg/kg, IP), or a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL; 0, 50 and 100 mg/kg, IP), attenuated METH-induced locomotor activity without affecting generalized behavior in METH naïve rats. PBN and TEMPOL significantly attenuated METH self-administration without affecting food intake. Increased oxidative stress was found in neurons, but not astrocytes, microglia or oligodendrocytes, in the NAc of METH self-administering rats. In addition, TEMPOL significantly decreased METH enhancement of DA release in the NAc. Taken together, these results suggest that enhancement of ROS in the NAc contributes to the reinforcing effect of METH.

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“…It was shown that METH increases the ROS production via various pathways [129, 130] including the inhibition of mitochondrial functions [131] and the stimulation of the NADPH oxidase (NOX) activity [132]. METH-induced ROS production is implicated in METH effects on neuronal degeneration [133, 134], toxicity in various cell types [135, 136], behavioral hyperactivity [137, 138], and hyperthermia [139, 140]. Notably, ROS-reducing agents including ROS scavengers and NOX inhibitors attenuate those effects of METH.…”

Section: Sig-1r-related Molecular Mechanisms and The Actions Of Cocaimentioning

confidence: 99%

Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine

Yasui

2016

J Drug Alcohol Res

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The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance.

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Subchronic apocynin treatment attenuates methamphetamine-induced dopamine release and hyperactivity in rats

Cited by 19 publications

References 29 publications

Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK

Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK

The role of reactive oxygen species in methamphetamine self-administration and dopamine release in the nucleus accumbens

Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine

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