Amphetamine Increases Phosphorylation of Extracellular Signal-regulated Kinase and Transcription Factors in the Rat Striatum via Group I Metabotropic Glutamate Receptors

Choe, Eun Sang; Chung, Kyung Tae; Mao, Limin; Wang, John Q.

doi:10.1016/s0893-133x(02)00341-x

Cited by 77 publications

(112 citation statements)

References 39 publications

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“…Moreover, short-term cocaine potentiates synaptic responses in ventral tegmental area dopamine neurons by promoting the rapid insertion of surface glutamate receptors (Borgland et al, 2004;Sun et al, 2008;Ferrario et al, 2011). ERK1/2 activation is also observed after amphetamine injections (Choe et al, 2002), and this requires both D1Rs and NMDARs (Valjent et al, 2005). The amphetamine-induced phosphorylation of ERK1/2 requires PKA-mediated phosphorylation of DARPP-32 and its subsequent inhibition of PP1 (Fig.…”

Section: G Drugs Of Abusementioning

confidence: 88%

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

Goebel-Goody

Baum²,

Paspalas³

et al. 2011

Pharmacol Rev

148

170

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Section: G Drugs Of Abusementioning

confidence: 88%

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

Goebel-Goody

Baum²,

Paspalas³

et al. 2011

Pharmacol Rev

148

170

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“…For example, we have shown that AMPH inhibits serine/threonine kinase Akt/protein kinase B (Garcia et al, 2005), and this might simply require intracellular AMPH and not DAT activity per se. Moreover, AMPH has been shown to activate extracellular signal-regulated kinase 1/2 (Choe et al, 2002) and PKC (Giambalvo, 1992a,b) and might directly modulate the activity of intracellular signal transduction cascades to regulate DAT membrane expression.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Dopamine Transporter Trafficking by Intracellular Amphetamine

Kahlig

Lute²,

Wei³

et al. 2006

Mol Pharmacol

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The dopamine (DA) transporter (DAT) mediates the removal of released DA. DAT is the major molecular target responsible for the rewarding properties and abuse potential of the psychostimulant amphetamine (AMPH). AMPH has been shown to reduce the number of DATs at the cell surface, and this AMPHinduced cell surface DAT redistribution may result in longlasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wildtype human DAT (WT-hDAT). However, AMPH did not induce cytosolic redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn 2ϩ ) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn 2ϩ and AMPH consistently reduced WThDAT trafficking but stimulated cytosolic redistribution of Y335A-hDAT. Furthermore, direct intracellular application of AMPH, via a whole-cell patch pipette, stimulated the trafficking of Y335A-hDAT. Taken together, these data suggest that the DAT transport cycle is not required for AMPH-induced downregulation and that an increase of intracellular AMPH is an essential component of DAT redistribution. Dopamine (DA) is a monoaminergic neurotransmitter involved in the control of locomotion, cognition, reward, and emotion (Iversen, 1971;Giros and Caron, 1993). The DA transporter (DAT) coordinates the spatial and temporal regulation of dopaminergic neurotransmission by mediating the reuptake of DA into presynaptic neurons. Although diffusion and enzymatic degradation contribute to reducing the synaptic concentration of DA, knockout studies have established DAT as the primary mechanism controlling extracellular DA levels (Giros et al., 1996;Jones et al., 1998). The regulatory mechanisms governing DAT are critical to DA signaling/ homeostasis. Altered dopaminergic signaling has been implicated in multiple brain disorders, including Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder, and addiction (Jucaite, 2002).DAT belongs to the Na ϩ /Cl Ϫ -dependent transporter gene family, which also consists of plasmalemmal carriers for the other monoamines, norepinephrine, epinephrine, and serotonin. Modulation of transporter surface expression may constitute a dynamic component of DA clearance (Melikian and Buckley, 1999;Loder and Melikian, 2003;Sorkina et al., 2005). Indeed, the clearance efficiency of DAT is determined not only by the transport rate of an individual transporter but also by the number of functional transporters on the cell surface. DAT trafficking has been shown to be regulated by receptor signaling, as well as by direct activation of protein

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“…Prior work has revealed that acute psychostimulant administration increases pERK and pCREB (Choe et al, 2002), and although any accompanying change in ⌬FosB is minimal, ⌬FosB is resistant to metabolism and is thus relatively more persistent (Nestler, 2004). With repeated injections, pERK and pCREB normalize or potentially "overcompensate" by decreasing levels, whereas ⌬FosB accumulates in brain tissue (Nestler, 2004).…”

Section: Downloaded Frommentioning

confidence: 99%

Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

McDaid

Graham²,

Napier

2006

Mol Pharmacol

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Enhancements in behavior that accompany repeated, intermittent administration of abused drugs (sensitization) endure long after drug administration has ceased. Such persistence reflects changes in intracellular signaling cascades and associated gene transcription factors in brain regions that are engaged by abused drugs. This process is not characterized for the most potent psychomotor stimulant, methamphetamine. Using motor behavior as an index of brain state in rats, we verified that five once-daily injections of 2.5 mg/kg methamphetamine induced behavioral sensitization that was demonstrated (expressed) 3 and 14 days later. Using immunoblot procedures, limbic brain regions implicated in behavioral sensitization were assayed for extracellular signal-regulated kinase and its phosphorylated form (pERK/ERK, a signal transduction kinase), cAMP response element binding protein and its phosphorylated form (pCREB/CREB, a constitutively expressed transcriptional regulator), and ⌬FosB (a long-lasting transcription factor). pERK, ERK, and CREB levels were not changed for any region assayed. In the ventral tegmental area, pCREB and ⌬FosB also were not changed. pCREB (activated CREB) was elevated in the frontal cortex at 3 days withdrawal, but not at 14 days. pCREB levels were decreased at 14 days withdrawal in the nucleus accumbens and ventral pallidum. Accumbal and pallidal levels of ⌬FosB were increased at 3 days withdrawal, and this increase persisted to 14 days in the pallidum. Thus, only the ventral pallidum showed changes in molecular processes that consistently correlated with motor sensitization, revealing that this region may be associated with this enduring behavioral phenotype initiated by methamphetamine. The present findings expand our understanding of the neuroanatomical and molecular substrates that may play a role in the persistence of druginduced sensitization.

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Amphetamine Increases Phosphorylation of Extracellular Signal-regulated Kinase and Transcription Factors in the Rat Striatum via Group I Metabotropic Glutamate Receptors

Abstract: Amphetamine is an indirect dopamine receptor agonist and increases glutamate release in the striatum. Activation of group I metabotropic glutamate receptors (mGluRs) upregulates cAMP response element-binding protein (CREB

Cited by 77 publications

References 39 publications

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders

Regulation of Dopamine Transporter Trafficking by Intracellular Amphetamine

Methamphetamine-Induced Sensitization Differentially Alters pCREB and ΔFosB throughout the Limbic Circuit of the Mammalian Brain

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