Neurotoxicity in Dopamine and 5‐Hydroxytryptamine Terminal Fields: A Regional Analysis in Nigrostriatal and Mesolimbic Projections

Seiden, Lewis S.; Commins, Deborah; Vosmer, Georgetta; Axt, Karen J.; Marek, Gerard J.

doi:10.1111/j.1749-6632.1988.tb42104.x

Cited by 116 publications

(84 citation statements)

References 30 publications

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“…Like other amphetamines, methamphetamine increases extracellular levels of monoamines by disrupting vesicular storage and reversing the plasma membrane transporter [262][263][264]. While methamphetamine's effects upon the monoaminergic systems have received considerable experimental attention [for reviews, [264][265][266][267][268][269][270], less is known regarding the regulation of corticoaccumbens glutamate and glutamate receptor expression by amphetamine and methylated analogs. Acute administration of amphetamines is reported to produce either no change or a delayed rise in extracellular glutamate levels within striatal regions [59][60][61][62]271,272], while an acute injection of methamphetamine, but not amphetamine, elevates PFC glutamate levels [271].…”

Section: Homers and Methamphetaminementioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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Section: Homers and Methamphetaminementioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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“…The nucleus accumbens (NAC) appears to be less vulnerable to the toxic effects of METH when compared to the CD/P. Although METH-induced neurotoxicity within the NAC has been reported to occur, a larger dose of METH is usually required to elicit these changes Seiden et al, 1988). In addition, degenerating terminals, visualized by silver staining, have been found within the core of the NAC (NACc), but not the shell (NACs) (Ricaurte et al, 1982), suggesting that METHinduced damage within the NAC itself may be heterogeneous.…”

Section: Introductionmentioning

confidence: 97%

Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate nucleus and motor cortex

Burrows

Meshul

1997

Synapse

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It has been suggested that methamphetamine (METH)-induced neurotoxicity requires the activation of both dopamine (DA) and glutamate (GLU) systems. To investigate the possibility that METH-induced increases in extracellular GLU, as measured by in vivo microdialysis [Nash and Yamamoto (1992) Brain Res., 581:237-243], arise from neuronal stores, postembedding immunogold electron microscopy was used to measure the density of presynaptic GLU immunoreactivity within the striatum, the shell of the nucleus accumbens, and the motor cortex. Rats were treated with METH (5 mg/kg), or an equivalent volume of saline (SAL), every 2 h for a total of four injections. No ultrastructural evidence of terminal degeneration was observed. Significant decreases in the density of nerve terminal GLU immunolabeling occurred 12 h following METH administration within the primary motor cortex and the ventrolateral caudate/putamen, and a trend towards depletion was seen within the dorsolateral caudate/putamen. Although GLU immunolabeling within the shell of the nucleus accumbens was unaffected, DA content was decreased in all regions examined 1 week following METH treatment. The lack of degeneration, coupled with a partial recovery of DA levels, suggests that moderate doses of METH may inhibit DA biosynthesis without widespread terminal loss. Furthermore, METH administration results in a decrease in presynaptic GLU that correlates both temporally and anatomically with delayed GLU overflow, suggesting that neuronally derived GLU may play a role in METH-induced neurotoxicity. However, there does appear to be a dissociation between DA loss and altered GLU immunocytochemistry within the nucleus accumbens.

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“…Methamphetamine (METH) is an abused psychostimulant that causes persistent damage to dopamine and serotonin terminals in the striatum, prefrontal cortex, and hippocampus Seiden et al, 1988;Wagner et al, 1980). The long-term dopamine and serotonin terminal damage is associated with numerous cognitive deficits exhibited by METH users and has more recently been shown to correlate with the potential for relapse of drug use (Clark et al, 2006;Johanson et al, 2006;Rogers et al, 1999;Simon et al, 2002;Volkow et al, 2001;Wang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Ammonia Mediates Methamphetamine-Induced Increases in Glutamate and Excitotoxicity

Halpin

Northrop

Yamamoto

2013

Neuropsychopharmacol

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Ammonia has been identified to have a significant role in the long-term damage to dopamine and serotonin terminals produced by methamphetamine (METH), but how ammonia contributes to this damage is unknown. Experiments were conducted to identify whether increases in brain ammonia affect METH-induced increases in glutamate and subsequent excitotoxicity. Increases in striatal glutamate were measured using in vivo microdialysis. To examine the role of ammonia in mediating changes in extracellular glutamate after METH exposure, lactulose was used to decrease plasma and brain ammonia. Lactulose is a non-absorbable disaccharide, which alters the intestinal lumen through multiple mechanisms that lead to the increased peripheral excretion of ammonia. METH caused a significant increase in extracellular glutamate that was prevented by lactulose. Lactulose had no effect on METH-induced hyperthermia. To determine if ammonia contributed to excitotoxicity, the effect of METH and lactulose treatment on calpain-mediated spectrin proteolysis was measured. METH significantly increased calpain-specific spectrin breakdown products, and this increase was prevented with lactulose treatment. To examine if ammonia-induced increases in extracellular glutamate were mediated by excitatory amino-acid transporters, the reverse dialysis of ammonia, the glutamate transporter inhibitor, DL-threo-b-benzyloxyaspartic acid (TBOA), or the combination of the two directly into the striatum of awake, freely moving rats was conducted. TBOA blocked the increases in extracellular glutamate produced by the reverse dialysis of ammonia. These findings demonstrate that ammonia mediates METH-induced increases in extracellular glutamate through an excitatory amino-acid transporter to cause excitotoxicity.

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Neurotoxicity in Dopamine and 5‐Hydroxytryptamine Terminal Fields: A Regional Analysis in Nigrostriatal and Mesolimbic Projections

Cited by 116 publications

References 30 publications

Homers regulate drug-induced neuroplasticity: Implications for addiction

Homers regulate drug-induced neuroplasticity: Implications for addiction

Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate nucleus and motor cortex

Ammonia Mediates Methamphetamine-Induced Increases in Glutamate and Excitotoxicity

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