Interactions of Dopamine, Glutamate, and GABA Systems in Mediating Amphetamine- and Cocaine-Induced Stereotypy and Behavioral Sensitization

Karler, Ralph; Thai, David K.; Calder, Larry D.

doi:10.1385/1-59259-306-2:107

Cited by 2 publications

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“…The results suggest a deficit of neuronal glutamate transporter in both cortical and subcortical regions of the brain. Our previous study identified an up‐regulation of NMDAR1 in the striatum and the frontal cortex after both acute and sub‐acute METH administrations , while another study showed increases in striatal GluR2 expression following acute METH , suggesting a compensatory response to deficits of glutamatergic function induced by METH . The current findings indicate the pathophysiological disturbance underlying this glutamatergic deficit and demonstrate some similarities to the changes observed in schizophrenia, in which NR1 increases are also associated with presynaptic glutamatergic deficits .…”

Section: Discussionsupporting

confidence: 71%

“…Dynamic changes in VGluT1 function and expression have been reported in the striatum and frontal cortex and which are related to METH‐induced glutamate release . Several studies have reported that excessive METH‐induced glutamate release in corticostriatal pathways contributes to the neurotoxic effects of METH , a finding likely to be a consequence of changes in the dopaminergic system induced by METH . Such METH‐induced neuronal degeneration may include effects on glutamatergic neurons and bring about a reduction in EAAT3, localized on both pre‐ and post‐synaptic neurons .…”

Section: Discussionmentioning

confidence: 99%

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Changes in the Neuronal Glutamate Transporter EAAT3 in Rat Brain after Exposure to Methamphetamine

Kerdsan

Thanoi

Nudmamud-Thanoi

2012

Basic Clin Pharma Tox

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Methamphetamine (METH), an addictive psychostimulant, can induce glutamate release in several brain areas such as cerebral cortex, hippocampus and striatum. Excess glutamate is ordinarily removed from the synaptic cleft by glutamate transporters for maintaining homoeostasis. EAAT3, a subtype of glutamate transporter expressed mainly by neurons, is a major glutamate transporter in the hippocampus and cortex. Therefore, this study examined the effects of acute and sub-acute METH administration on the expression of the EAAT3 in the hippocampal formation, striatum and frontal cortex. Male Sprague-Dawley rats received vehicle injections (i.p.) for 13 days followed by one injection of METH (8 mg/kg, i.p.) on day 14 in acute group. Animals received METH (4 mg/kg, i.p.) or vehicle for 14 days in sub-acute and control groups, respectively. EAAT3 immunoreactivity was determined by western blotting followed by measurement of the integrated optical density. A significant increase in EAAT3 was found in the hippocampal formation after sub-acute, but not acute, METH administration. Conversely, a significant decrease in EAAT3 in striatum was observed in both acute and sub-acute groups. A trend towards a decrease in EAAT3 was also found in frontal cortex in the sub-acute group. Our results of decreased EAAT3 in striatum and frontal cortex suggest deficits of cortico-striatal glutamatergic synapses after METH exposure. Increased EAAT3 expression in the hippocampus may be a compensatory response to possible deficits of glutamatergic neurotransmission induced by METH. Moreover, our findings provide further support for glutamatergic dysfunction with abnormalities involving a transporter important in the regulation of neuronal glutamate.Methamphetamine (METH) is an addictive psychostimulant with potent effects on the central nervous system (CNS) [1,2]. METH has been reported to have a major impact on both cortical and subcortical regions of brain [3,4]. Several studies have shown neurotoxic effects of METH on dopaminergic and serotonergic systems [5,6]. Dysfunctions of dopaminergic neurotransmission such as fibre degeneration, abnormalities of dopamine transporter and tyrosine hydroxylase as well as depletion of dopamine content have been observed following METH exposure [7][8][9][10]. In addition, METH-induced dopamine depletion is blocked by glutamate N-methyl-D-aspartate (NMDA) receptor antagonism [11]. This has led to a hypothesis that the glutamatergic system may be implicated in the neurotoxic effect of METH. Glutamatergic effects of METH exposure have also been reported. METH-induced glutamate release was observed in several brain regions, such as striatum [12], cerebral cortex [13], hippocampus [14], ventral tegmental area and nucleus accumbens [15]. Excess extracellular glutamate can stimulate glutamate receptors such as NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, potentially leading to neurotoxicity [16][17][18]. An up-regulation of NMDAR1 and AMPA GluR2 subunits after METH...

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Changes in the Neuronal Glutamate Transporter EAAT3 in Rat Brain after Exposure to Methamphetamine

Kerdsan

Thanoi

Nudmamud-Thanoi

2012

Basic Clin Pharma Tox

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“…As METH is an abused psychostimulant, our results provide a support for effects of these drugs on glutamatergic systems. Glutamatergic dysfunctions may be a consequence of changes in the dopaminergic system induced by psychostimulants [ 16 ]. Moreover, an impairment of monoamine neurotransmission after repeated METH exposure can produce changes in amino acid homeostasis, potentially leading to neurotoxicity [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

Kerdsan

Thanoi

Nudmamud-Thanoi

2009

BioMed Research International

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Methamphetamine (METH) is a psychostimulant drug of abuse that produces long-term behavioral changes including behavioral sensitization, tolerance, and dependence. METH has been reported to induce neurotoxic effects in several areas of the brain via the dopaminergic system. Changes of dopamine function can induce malfunction of the glutamatergic system. Therefore, the aim of the present study was to examine the effects of METH administration on the expression of glutamate N-methyl-D-aspartate receptor subunit 1 (NMDAR1) in frontal cortex, striatum, and hippocampal formation after acute and subacute exposure to METH by western blotting. Male Sprague-Dawley rats were injected intraperitoneally with a single dose of 8 mg/kg METH, 4 mg/kg/day METH for 14 days and saline in acute, subacute, and control groups, respectively. A significant increase in NMDAR1 immunoreactive protein was found in frontal cortex in the subacute group (P = .036) but not in the acute group (P = .580). Moreover, a significant increase in NMDAR1 was also observed in striatum in both acute (P = .025) and subacute groups (P = .023). However, no significant differences in NMDAR1 in hippocampal formation were observed in either acute or subacute group. The results suggest that an upregulation of NMDA receptor expression may be a consequence of glutamatergic dysfunction induced by METH.

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Interactions of Dopamine, Glutamate, and GABA Systems in Mediating Amphetamine- and Cocaine-Induced Stereotypy and Behavioral Sensitization

Cited by 2 publications

References 0 publications

Changes in the Neuronal Glutamate Transporter EAAT3 in Rat Brain after Exposure to Methamphetamine

Changes in the Neuronal Glutamate Transporter EAAT3 in Rat Brain after Exposure to Methamphetamine

Changes in Glutamate/NMDA Receptor Subunit 1 Expression in Rat Brain after Acute and Subacute Exposure to Methamphetamine

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