Cortical glutamate–dopamine interaction and ketamine-induced psychotic symptoms in man

Aalto, Sargo; Ihalainen, Jouni; Hirvonen, Jussi; Kajander, Jaana; Scheinin, Harry; Tanila, Heikki; Någren, Kjell; Vilkman, Harry; Gustafsson, Lars L.; Syvälahti, Erkka; Hietala, Jarmo

doi:10.1007/s00213-005-0092-6

Cited by 82 publications

(60 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, this decrease in [ 11 C]-raclopride binding was similar to the decrease shown after amphetamine administration (Breier et al, 1998). Others (Smith et al, 1998;Vollenweider et al, 2000;Aalto et al, 2005) have also documented this interaction, concluding that glutamatergic antagonism is associated to an increase of dopamine release in the cerebral cortex and the striatum, and inducing positive and negative symptoms similar to those observed in schizophrenia. In addition, NMDA-receptor blockade in healthy humans has been shown to increase Gln levels in the anterior cingulate as measured by 1 H-MRS (Rowland et al, 2005).…”

Section: Glutamate-dopamine Interaction and Schizophreniasupporting

confidence: 73%

“…Single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies in humans have provided evidence that non-competitive glutamate NMDA receptor antagonists, such as ketamine, increase amphetamine-induced dopamine release (Kegeles et al, 2000), and decrease D 2/3 binding in the posterior cingulate cortex (Aalto et al, 2005) and striatum (Breier et al, 1998;Smith et al, 1998;Vollenweider et al, 2000). Other studies though have not supported this finding in the striatum (Aalto et al, 2002;Kegeles et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

View full text Add to dashboard Cite

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ( 1 H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first-episode psychosis patients (FEP), and (3) 40 age-and sex-matched healthy controls. All subjects underwent a 1 H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

show abstract

Section: Glutamate-dopamine Interaction and Schizophreniasupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Fuente‐Sandoval

León-Ortíz

Favila

et al. 2011

Neuropsychopharmacol

208

157

View full text Add to dashboard Cite

show abstract

“…This was supported by the finding that acute application of NMDAR antagonist stimulates dopamine release in animal models [91] and humans [92,93] (but see Ref. [94]).…”

Section: The Hyperdopaminergic State and The Role Of The Hippocampusmentioning

confidence: 86%

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Lisman

Coyle

Green

et al. 2008

Trends in Neurosciences

899

824

View full text Add to dashboard Cite

Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.

show abstract

“…Systemic administration of these drugs to rodents and nonhuman primates produces behavioral deficits that parallel some positive and negative symptoms, as well as the cognitive deficits of schizophrenia (Bakshi and Geyer 1998;Hauber and Andersen 1993;Jentsch et al 1997;Stefani and Moghaddam 2005;Verma and Moghaddam 1996). At a cellular level, NMDA antagonist administration increases dopamine release in the prefrontal cortex (PFC) of rodents (Verma and Moghaddam 1996) and humans (Aalto et al 2005), suggesting that they work, in part, by disrupting dopamine neurotransmission.…”

mentioning

confidence: 99%

Positive Allosteric Modulation of Metabotropic Glutamate 5 (mGlu5) Receptors Reverses N-Methyl-D-Aspartate Antagonist-Induced Alteration of Neuronal Firing in Prefrontal Cortex

Lecourtier

Homayoun

Tamagnan

et al. 2007

Biological Psychiatry

View full text Add to dashboard Cite

Background-Several lines of evidence suggest that N-methyl-D-aspartate (NMDA) receptor hypofunction may be associated with schizophrenia. Activation of metabotropic glutamate 5 (mGlu5) receptors enhances NMDA receptor mediated currents in vitro, implying that allosteric modulation of mGlu5 receptors may have therapeutic efficacy for schizophrenia. The aim of this study was to determine if positive allosteric modulators of mGlu5 receptors are effective in reversing two cellular effects of NMDA receptor antagonists that are relevant to schizophrenia: increases in corticolimbic dopamine neurotransmission and disruption of neuronal activity in the prefrontal cortex (PFC).

show abstract

Cortical glutamate–dopamine interaction and ketamine-induced psychotic symptoms in man

Cited by 82 publications

References 70 publications

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Higher Levels of Glutamate in the Associative-Striatum of Subjects with Prodromal Symptoms of Schizophrenia and Patients with First-Episode Psychosis

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Positive Allosteric Modulation of Metabotropic Glutamate 5 (mGlu5) Receptors Reverses N-Methyl-D-Aspartate Antagonist-Induced Alteration of Neuronal Firing in Prefrontal Cortex

Contact Info

Product

Resources

About