a(CHEBI:methamphetamine)

Entity

Name

methamphetamine

Namespace

chebi

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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