Drugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons

Saal, Daniel; Dong, Yan; Bonci, Antonello; Malenka, Robert C.

doi:10.1016/s0896-6273(03)00021-7

Cited by 1,036 publications

(985 citation statements)

References 33 publications

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“…The same dose of amphetamine was also sufficient to increase the AMPAR/NMDAR ratios at the glutamatergic synapses in the VTA 24 h later. Our observations are consistent with those reported recently for amphetamine and several other drugs of abuse (Ungless et al, 2001;Saal et al, 2003). In the hippocampus, an increase in the AMPAR component of the excitatory postsynaptic response occurs at synapses that have undergone LTP (Kauer et al, 1988;Isaac et al, 1995;Liao et al, 1995;Malinow and Malenka, 2002).…”

Section: A Single Dose Of Amphetamine Alters Glutamatergic Synapses Isupporting

confidence: 92%

“…This result is consistent with those previously reported in response to cocaine and amphetamine (Vanderschuren et al, 1999;Ungless et al, 2001;Saal et al, 2003). The same dose of amphetamine was also sufficient to increase the AMPAR/NMDAR ratios at the glutamatergic synapses in the VTA 24 h later.…”

Section: A Single Dose Of Amphetamine Alters Glutamatergic Synapses Isupporting

confidence: 92%

“…We and others have observed changes in the behavior of glutamatergic synapses in the VTA 24 h after exposure to amphetamine (Saal et al, 2003). We wanted to know whether the changes in AMPAR/NMDAR ratios are a consequence of a 24 h-long cascade of events or whether they represent a relatively rapid response to amphetamine, similar to hippocampal LTP, which can develop within minutes.…”

Section: Resultsmentioning

confidence: 99%

“…Several lines of evidence support the idea that synaptic plasticity at glutamate synapses in the VTA plays a key role in triggering sensitization and other neuroadaptations that may contribute to the development of addiction (Schenk and Snow, 1994;White, 1996;Carlezon et al, 1997;Ungless et al, 2001;Hyman and Malenka, 2001;Kauer, 2004). Most recently it has been demonstrated that the glutamate receptor complement (AMPAR/NMDAR ratio) at excitatory synapses onto VTA DA neurons is altered 24 h after exposure to several distinct drugs of abuse, but not by centrally acting drugs that are not addictive (Ungless et al, 2001;Saal et al, 2003). Together, the data indicate that 24 h after a single exposure to an addictive drug, alterations in excitatory synapses can be observed that are consistent with long-term potentiation.…”

Section: Introductionmentioning

confidence: 91%

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Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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Section: A Single Dose Of Amphetamine Alters Glutamatergic Synapses Isupporting

confidence: 92%

Section: A Single Dose Of Amphetamine Alters Glutamatergic Synapses Isupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

See 2 more Smart Citations

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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“…In vivo administration of drugs of abuse with different molecular mechanisms of action as well as acute stress do, in fact, elicit LTP at excitatory synapses on VTA dopamine neurons (Bonci and Malenka, 1999;Ungless et al, 2001;Saal et al, 2003). The response to cocaine and stress have also been shown to require NMDAR activation (Shors and Servatius, 1995;Li et al, 1999;Thomas et al, 2001;Borgland et al, 2004).…”

Section: Nmdar-dependent Ltp Of Field Potentials Presents a Simpler Mmentioning

confidence: 99%

High-Frequency Afferent Stimulation Induces Long-Term Potentiation of Field Potentials in the Ventral Tegmental Area

Nugent

Hwong

Udaka

et al. 2007

Neuropsychopharmacol

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Excitatory synapses on dopamine neurons in the VTA can undergo both long-term potentiation and depression. Additionally, druginduced plasticity has been found at VTA synapses, and is proposed to play a role in reward-related learning and addiction by modifying dopamine cell firing. LTP at these synapses is difficult to generate experimentally in that it requires an undisturbed intracellular milieu and is often small in magnitude. Here, we demonstrate the induction of LTP as a property of evoked field potentials within the VTA. Excitatory field potentials were recorded extracellularly from VTA neurons in acute horizontal midbrain slices. Using extracellular and intracellular recording techniques, we found that evoked field potentials originate within the VTA itself and are largely composed of AMPA receptor-mediated EPSPs and action potentials triggered by activation of glutamatergic synapses on both dopamine and GABA neurons. High-frequency afferent stimulation (HFS) induced LTP of the field potential. The induction of this LTP was blocked by application of the NMDAR antagonist, d-APV, prior to HFS. As reported previously, glutamatergic synapses on GABA neurons did not express LTP while those on dopamine neurons did. We conclude that the potentiation of glutamatergic synapses on dopamine neurons is a major contributor to NMDA receptor-dependent LTP of the field potential. Field potential recordings may provide a convenient approach to explore the basic electrophysiological properties of VTA neurons and the development of addiction-related processes in this brain region.

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A Twin Registry Study of the Relationship Between Posttraumatic Stress Disorder and Nicotine Dependence in Men

Koenen¹,

Hitsman²,

Lyons³

et al. 2005

Arch Gen Psychiatry

185

128

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Most of the PTSD-ND association is explained by shared genetic effects. However, there is a substantial, robust PTSD-ND association not explained by shared risk factors. Multiple explanations for the association were supported; however, the strongest association was consistent with preexisting ND increasing the risk of PTSD onset. These data suggest that male veterans with a history of ND may be at increased risk for PTSD. Further research on the biological mechanisms underlying PTSD-ND comorbidity is needed.

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Drugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons

Cited by 1,036 publications

References 33 publications

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

High-Frequency Afferent Stimulation Induces Long-Term Potentiation of Field Potentials in the Ventral Tegmental Area

A Twin Registry Study of the Relationship Between Posttraumatic Stress Disorder and Nicotine Dependence in Men

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