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Entity

Name
methamphetamine
Namespace
chebi
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

Appears in Networks 3

In-Edges 10

act(a(CHEBI:nicotine)) decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

For example, nicotine effectively protects wild-type mice, but not alpha4-knockout mice, against methamphetamine-evoked neurodegeneration (Ryan et al., 2001). PubMed:19293145

a(CHEBI:"(-)-lobeline") decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

Lobeline has, however, been shown to antagonize partially the stimulus effects of (-)-nicotine and S(+)-methamphetamine ([64, 160]; but see [66]). PubMed:28391535

sec(a(CHEBI:dopamine)) association a(CHEBI:methamphetamine) View Subject | View Object

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

a(CHEBI:sirolimus) decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

In fact, mTOR-induced autophagy inhibition exacerbates the ultrastructural effects of METH [126,134–136], while rapamycin administration reverts both behavioral and morphological alterations induced by METH [137]. PubMed:30061532

bp(GO:"dopamine secretion, neurotransmission") association a(CHEBI:methamphetamine) View Subject | View Object

These findings strongly suggest that an autophagy dysfunction acts both at pre- and post-synaptic level to alter DA neurotransmission during both METH administration and schizophrenia (Figure 2) PubMed:30061532

bp(GO:autophagy) decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

In fact, mTOR-induced autophagy inhibition exacerbates the ultrastructural effects of METH [126,134–136], while rapamycin administration reverts both behavioral and morphological alterations induced by METH [137]. PubMed:30061532

bp(GO:autophagy) decreases act(a(CHEBI:methamphetamine)) View Subject | View Object

This confirms our previous studies showing that both genetic and pharmacological autophagy inhibition worsen the effects of METH administration PubMed:30061532

p(HGNC:DRD1) association a(CHEBI:methamphetamine) View Subject | View Object

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

act(p(HGNC:MTOR)) increases act(a(CHEBI:methamphetamine)) View Subject | View Object

In fact, mTOR-induced autophagy inhibition exacerbates the ultrastructural effects of METH [126,134–136], while rapamycin administration reverts both behavioral and morphological alterations induced by METH [137]. PubMed:30061532

p(HGNC:SLC18A2) negativeCorrelation a(CHEBI:methamphetamine) View Subject | View Object

A reduction in VMAT-2 gene expression and protein levels in DA neurons occurs in both METH models and schizophrenic patients, marking quite impressively the overlap between these disorders PubMed:30061532

Out-Edges 25

act(a(CHEBI:methamphetamine)) increases bp(HBP:Neurodegeneration) View Subject | View Object

For example, nicotine effectively protects wild-type mice, but not alpha4-knockout mice, against methamphetamine-evoked neurodegeneration (Ryan et al., 2001). PubMed:19293145

a(CHEBI:methamphetamine) decreases bp(GO:"dopamine secretion, neurotransmission") View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) association bp(GO:"dopamine secretion, neurotransmission") View Subject | View Object

These findings strongly suggest that an autophagy dysfunction acts both at pre- and post-synaptic level to alter DA neurotransmission during both METH administration and schizophrenia (Figure 2) PubMed:30061532

a(CHEBI:methamphetamine) decreases bp(GO:autophagy) View Subject | View Object

In line with this, METH produces ultrastructural alterations reflecting dysfunctional autophagy flux, which are DA-dependent PubMed:30061532

a(CHEBI:methamphetamine) decreases act(p(HGNCGENEFAMILY:"Dopamine receptors")) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) decreases act(p(HGNC:DRD1)) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) association p(HGNC:DRD1) View Subject | View Object

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

a(CHEBI:methamphetamine) increases bp(GO:"non-canonical Wnt signaling pathway") View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) increases path(MESH:Hallucinations) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) increases path(MESH:Delusions) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

a(CHEBI:methamphetamine) decreases act(g(HGNC:DISC1)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

a(CHEBI:methamphetamine) decreases act(g(HGNC:NRG1)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

a(CHEBI:methamphetamine) decreases act(g(HGNC:DPYSL2)) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

a(CHEBI:methamphetamine) increases path(MESH:"Psychoses, Substance-Induced") View Subject | View Object

In humans, the sensitizing effects of prolonged chronic METH intake are considered a major determinant to the occurrence and relapse of psychoses, which mirror those occurring in schizophrenic patients PubMed:30061532

a(CHEBI:methamphetamine) decreases act(p(HGNC:SLC6A3)) View Subject | View Object

Such an abnormal DA release produces peaks of extracellular DA, which cannot be taken up within nerve terminals, because METH inhibits and reverts the direction of the dopamine transporter (DAT). PubMed:30061532

a(CHEBI:methamphetamine) decreases p(HGNC:SLC6A3) View Subject | View Object

In line with this, recent studies suggest that DAT expression is significantly reduced in the midbrain of postmortem schizophrenic samples [150], which is reminiscent of the METH-addicted brain [151,152]. PubMed:30061532

a(CHEBI:methamphetamine) decreases a(CHEBI:dopamine, loc(MESH:"Nerve Endings")) View Subject | View Object

Such an abnormal DA release produces peaks of extracellular DA, which cannot be taken up within nerve terminals, because METH inhibits and reverts the direction of the dopamine transporter (DAT). PubMed:30061532

a(CHEBI:methamphetamine) decreases sec(a(CHEBI:dopamine)) View Subject | View Object

These findings strongly suggest that an autophagy dysfunction acts both at pre- and post-synaptic level to alter DA neurotransmission during both METH administration and schizophrenia (Figure 2) PubMed:30061532

a(CHEBI:methamphetamine) increases a(CHEBI:dopamine, loc(GO:cytosol)) View Subject | View Object

In fact, METH produces a massive increase of endogenous intra-cytosolic DA levels by inhibiting and reverting the direction of the vesicular monoamine transporter type 2 (VMAT-2), thus disrupting the physiological storage of DA PubMed:30061532

a(CHEBI:methamphetamine) association sec(a(CHEBI:dopamine)) View Subject | View Object

In line with this, experimental models of DISC1 deficiency treated with METH show a significant potentiation of DA release, along with increased expression of D1R in the ventral striatum when compared with controls PubMed:30061532

a(CHEBI:methamphetamine) decreases act(p(HGNC:SLC18A2)) View Subject | View Object

In fact, METH produces a massive increase of endogenous intra-cytosolic DA levels by inhibiting and reverting the direction of the vesicular monoamine transporter type 2 (VMAT-2), thus disrupting the physiological storage of DA PubMed:30061532

a(CHEBI:methamphetamine) negativeCorrelation p(HGNC:SLC18A2) View Subject | View Object

A reduction in VMAT-2 gene expression and protein levels in DA neurons occurs in both METH models and schizophrenic patients, marking quite impressively the overlap between these disorders PubMed:30061532

a(CHEBI:methamphetamine) increases bp(GO:"response to oxidative stress") View Subject | View Object

It is worth mentioning that freely diffusible intra-cytosolic DA can readily undergo auto-oxidation and produce a cascade of oxidative-related damage, which is bound to the neurotoxic effects of high doses of METH PubMed:30061532

a(CHEBI:methamphetamine) increases act(p(FPLX:AKT)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

a(CHEBI:methamphetamine) increases act(p(HGNC:MTOR)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.