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Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
- B. Moghaddam, B. Adams, A. Verma, D. Daly
- Biology, PsychologyThe Journal of Neuroscience
- 15 April 1997
The findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.
Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats.
Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model, and an agonist of this group of receptors attenuated the disruptive effects of Phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux.
NMDA Receptor Hypofunction Produces Opposite Effects on Prefrontal Cortex Interneurons and Pyramidal Neurons
Findings support the hypothesis that NMDA receptor hypofunction, which has been implicated in the pathophysiology of schizophrenia, diminishes the inhibitory control of PFC output neurons and may be critical for treatment of schizophrenia.
Corticolimbic Dopamine Neurotransmission Is Temporally Dissociated from the Cognitive and Locomotor Effects of Phencyclidine
It is indicated that activation of dopamine neurotransmission is not sufficient to sustain PCP-induced locomotion and impairment of working memory, and effects of PCP, including a glutamatergic hyperstimulation, may be necessary to account for the psychotomimetic and cognitive-impairing effects of this drug.
From Revolution to Evolution: The Glutamate Hypothesis of Schizophrenia and its Implication for Treatment
NMDAR has intrinsic modulatory sites that are active targets for drug development, several of which show promise in preclinical/early clinical trials targeting both symptoms and cognition, and allosteric modulators, both positive and negative, may offer superior efficacy with less danger of downregulation.
NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex.
- M. Jackson, H. Homayoun, B. Moghaddam
- Psychology, BiologyProceedings of the National Academy of Sciences…
- 1 June 2004
Using ensemble recording in freely moving rats, it is found that NMDA antagonist treatment, at doses that impaired working memory, potentiated the firing rate of most prefrontal cortex neurons, which provides a physiological basis for the NMDA receptor deficiency model of schizophrenia and may clarify the nature of cortical dysfunction in this disease.
Ionic Composition of Microdialysis Perfusing Solution Alters the Pharmacological Responsiveness and Basal Outflow of Striatal Dopamine
Perfusion with solutions containing the ionic composition of commercially available Ringer's solution, which mimic the ional composition of plasma as opposed to brain extracellular fluid, alters the turnover rate and basal release of dopamine.
The Prefrontal Cortex Regulates the Basal Release of Dopamine in the Limbic Striatum: An Effect Mediated by Ventral Tegmental Area
It is demonstrated that the basal output of dopamine terminals in the medial striatum is under a tonic excitatory control of the PFC, and this control occurs primarily through glutamatergic projections to the dopamine cell body area rather than the terminal regions.
NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: modulation by dopamine
Findings indicate that attenuation of glutamatergic neurotransmission at the NMDA receptor impairs PFC- dependent cognitive functions and activation of dopamine neurotransmission contributes, at least in part, to this impairment.
Stress Preferentially Increases Extraneuronal Levels of Excitatory Amino Acids in the Prefrontal Cortex: Comparison to Hippocampus and Basal Ganglia
- B. Moghaddam
- BiologyJournal of neurochemistry
- 1 May 1993
Direct evidence is provided that stress increases the neuronal release of excitatory amino acids in a regionally selective manner, i.e., striatum and medial prefrontal cortex, which is associated with hippocampal degeneration.