In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

Huang, Wen-Sheng; Chen, Guann-Juh; Tsai, Tung-Han; Cheng, Chen-Yi; Shiue, Chyng‐Yann; Ma, Kuo‐Hsing; Yeh, Skye Hsin-Hsien

doi:10.1186/s13550-019-0557-y

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…In this study, serum serotonin was reduced after MA treatment, implying its close association with MA-induced intestinal inflammation. Furthermore, MA can result in serotonin depletion and further influence locomotor sensitization ( Huang et al, 2019 ), which were in accordance with our results. Knockout of serotonin transporter inhibits MA-induced locomotor sensitization, which is restored by selective 5-HT1B antagonist receptor ( Igari et al, 2015 ).…”

Section: Discussionsupporting

confidence: 92%

Methamphetamine Disturbs Gut Homeostasis and Reshapes Serum Metabolome, Inducing Neurotoxicity and Abnormal Behaviors in Mice

Zhang

Chen

et al. 2022

Front. Microbiol.

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As an illicit psychostimulant, repeated methamphetamine (MA) exposure results in addiction and causes severe neurotoxicity. Studies have revealed complex interactions among gut homeostasis, metabolism, and the central nervous system (CNS). To investigate the disturbance of gut homeostasis and metabolism in MA-induced neurotoxicity, 2 mg/kg MA or equal volume saline was intraperitoneally (i.p.) injected into C57BL/6 mice. Behavioral tests and western blotting were used to evaluate neurotoxicity. To determine alterations of colonic dysbiosis, 16s rRNA gene sequencing was performed to analyze the status of gut microbiota, while RNA-sequencing (RNA-seq) and Western Blot analysis were performed to detect colonic damage. Serum metabolome was profiled by LC–MS analysis. We found that MA induced locomotor sensitization, depression-, and anxiety-like behaviors in mice, along with dysfunction of the dopaminergic system and stimulation of autophagy as well as apoptosis in the striatum. Notably, MA significantly decreased microbial diversity and altered the component of microbiota. Moreover, findings from RNA-seq implied stimulation of the inflammation-related pathway after MA treatment. Western blotting confirmed that MA mediated colonic inflammation by activating the TLR4-MyD88-NF-κB pathway and impaired colonic barrier. In addition, serum metabolome was reshaped after MA treatment. Specifically, bacteroides-derived sphingolipids and serotonin were obviously altered, which were closely correlated with locomotor sensitization, depression-, and anxiety-like behaviors. These findings suggest that MA disrupts gut homeostasis by altering its microbiome and arousing inflammation, and reshapes serum metabolome, which provide new insights into understanding the interactions between gut homeostasis and MA-induced neurotoxicity.

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Section: Discussionsupporting

confidence: 92%

Methamphetamine Disturbs Gut Homeostasis and Reshapes Serum Metabolome, Inducing Neurotoxicity and Abnormal Behaviors in Mice

Zhang

Chen

et al. 2022

Front. Microbiol.

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“…Although chronic meth administration did not result in serotonergic degeneration, studies using an acute binge model of meth administration produce serotonin depletion (Hotchkiss and Gibb, 1980;Peat et al, 1985;Commins and Seiden, 1986;Ricaurte et al, 1989;Schmidt et al, 1991;Green et al, 1992;Pu and Vorhees, 1995) and decreased activity of SERT (Haughey et al, 2000;Sekine et al, 2006;Kish et al, 2010;Huang et al, 2019) and TPH (Hotchkiss and Gibb, 1980), whereas, 32 mg/kg/day for 5 days produces a decrease in 5-HT uptake sites (Armstrong and Noguchi, 2004); for review see Krasnova and Cadet (2009). These results are not inherently in conflict with our findings as tissue content of neurotransmitter, protein expression, and/or protein function are not necessarily 10.3389/fncel.2022.949923 indicative of degeneration or degenerative processes.…”

Section: Discussionmentioning

confidence: 99%

Differential vulnerability of locus coeruleus and dorsal raphe neurons to chronic methamphetamine-induced degeneration

Choi

Pilski

et al. 2022

Front. Cell. Neurosci.

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Methamphetamine (meth) increases monoamine oxidase (MAO)-dependent mitochondrial stress in axons of substantia nigra pars compacta (SNc), and ventral tegmental area (VTA) dopamine neurons. Chronic administration of meth results in SNc degeneration and MAO inhibition is neuroprotective, whereas, the VTA is resistant to degeneration. This differential vulnerability is attributed, at least in part, to the presence of L-type Ca2+ channel-dependent mitochondrial stress in SNc but not VTA dopamine neurons. MAO is also expressed in other monoaminergic neurons such as noradrenergic locus coeruleus (LC) and serotonergic dorsal raphe (DR) neurons. The impact of meth on mitochondrial stress in LC and DR neurons is unknown. In the current study we used a genetically encoded redox biosensor to investigate meth-induced MAO-dependent mitochondrial stress in LC and DR neurons. Similar to SNc and VTA neurons, meth increased MAO-dependent mitochondrial stress in axonal but not somatic compartments of LC norepinephrine and DR serotonin neurons. Chronic meth administration (5 mg/kg; 28-day) resulted in degeneration of LC neurons and MAO inhibition was neuroprotective whereas DR neurons were resistant to degeneration. Activating L-type Ca2+ channels increased mitochondrial stress in LC but not DR axons and inhibiting L-type Ca2+ channels in vivo with isradipine prevented meth-induced LC degeneration. These data suggest that similar to recent findings in SNc and VTA dopamine neurons, the differential vulnerability between LC and DR neurons can be attributed to the presence of L-type Ca2+ channel-dependent mitochondrial stress. Taken together, the present study demonstrates that both meth-induced MAO- and L-type Ca2+ channel-dependent mitochondrial stress are necessary for chronic meth-induced neurodegeneration.

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“…There are putative concerns specific to methamphetamine; the predominant mechanism of action of methamphetamine is to elevate the concentration of the monoamines dopamine and norepinephrine within the synaptic cleft through substrate-based release and interrupted reuptake (77,78). There are studies showing that crosstalk between the dopamine and noradrenergic systems with the serotonin system can lead to significant changes in serotonin transporters and receptors (79)(80)(81)(82). This could modify the response to psilocybin, which, via its active metabolite psilocin, acts at 5-HT 2A receptors and other 5-HT receptors.…”

Section: Dosagementioning

confidence: 99%

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder

Brett

Knock²,

Korthuis³

et al. 2023

Front. Psychiatry

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Methamphetamine use disorder is a chronic relapsing condition associated with substantial mental, physical, and social harms and increasing rates of mortality. Contingency management and psychotherapy interventions are the mainstays of treatment but are modestly effective with high relapse rates, while pharmacological treatments have shown little to no efficacy. Psilocybin-assisted psychotherapy is emerging as a promising treatment for a range of difficult-to-treat conditions, including substance use disorders; however, no studies have yet been published looking at psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Here we review the rationale for psilocybin-assisted psychotherapy as a potential treatment for this indication, and describe practical considerations based on our early experience designing and implementing four separate clinical trials of psilocybin-assisted psychotherapy for methamphetamine use disorder.

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In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

Cited by 6 publications

References 44 publications

Methamphetamine Disturbs Gut Homeostasis and Reshapes Serum Metabolome, Inducing Neurotoxicity and Abnormal Behaviors in Mice

Methamphetamine Disturbs Gut Homeostasis and Reshapes Serum Metabolome, Inducing Neurotoxicity and Abnormal Behaviors in Mice

Differential vulnerability of locus coeruleus and dorsal raphe neurons to chronic methamphetamine-induced degeneration

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder

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