Psychosis pathways converge via D2High dopamine receptors

@article{Seeman2006PsychosisPC,
  title={Psychosis pathways converge via D2High dopamine receptors},
  author={Philip Seeman and Johannes Schwarz and Jiang-fan Chen and Henry Szechtman and Melissa L. Perreault and G. Stanley McKnight and John C. Roder and Rémi Quirion and Patricia Boksa and Lalit K Srivastava and Kazuhiko Yanai and David Weinshenker and Tomiki Sumiyoshi},
  journal={Synapse},
  year={2006},
  volume={60}
}
The objective of this review is to identify a target or biomarker of altered neurochemical sensitivity that is common to the many animal models of human psychoses associated with street drugs, brain injury, steroid use, birth injury, and gene alterations. Psychosis in humans can be caused by amphetamine, phencyclidine, steroids, ethanol, and brain lesions such as hippocampal, cortical, and entorhinal lesions. Strikingly, all of these drugs and lesions in rats lead to dopamine supersensitivity… 

All Roads to Schizophrenia Lead to Dopamine Supersensitivity and Elevated Dopamine D2High Receptors

  • P. Seeman
  • Psychology, Medicine
    CNS neuroscience & therapeutics
  • 2011
TLDR
Why individuals with schizophrenia are generally supersensitive to dopamine‐like drugs such as amphetamine or methyphenidate is reviewed and whether the D2High state is a common basis for dopamine supersensitivity in the animal models of schizophrenia is reviewed.

All Psychotic Roads Lead to Increased Dopamine D2High Receptors: A Perspective

TLDR
Animal models of schizophrenia show dopamine supersensitivity, but surprisingly, no increase in dopamine D2 receptors, while proposed animal models of psychosis and their dopaminergic abnormalities reveal elevations in D2High.

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  • P. Seeman
  • Psychology, Medicine
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2013

Dopamine D2 receptors as treatment targets in schizophrenia.

  • P. Seeman
  • Psychology, Medicine
    Clinical schizophrenia & related psychoses
  • 2010
TLDR
Animal models of psychosis show that a variety of risk factors, genetic and nongenetic, are associated with behavioral supersensitivity to dopamine, reflected in elevated levels of dopamine D2High receptors, and long-term use of traditional antipsychotics can further enhance dopamine supersensitivity in patients.

Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

TLDR
It is found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons, and amphetamine-induced D2 Rs dimerized may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D 2R- DAT coupling.

Historical Overview: Introduction to the Dopamine Receptors

TLDR
The elevation of D2 High receptors may be the unifying mechanism for the various causes of schizophrenia.

Alterations of Dopamine D2 Receptors and Related Receptor-Interacting Proteins in Schizophrenia: The Pivotal Position of Dopamine Supersensitivity Psychosis in Treatment-Resistant Schizophrenia

TLDR
Data strongly suggest that the continuous blockade of DRD2 by antipsychotic(s) could eventually fail to control the psychosis in some point during long-term treatment, even if such treatment has successfully provided symptomatic improvement for the first-episode psychosis, or stability for the subsequent chronic stage.

Applications of the Neonatal Quinpirole Model to Psychosis and Convergence upon the Dopamine D2 Receptor.

TLDR
The importance of the combination of behavioral findings and neurobiological mechanisms focusing on neural plasticity in discovering underlying pathologies in these disorders that may lead to treatment discoveries, as well as the value of animal models across all psychoses are highlighted.

Dopamine partial agonist action of (-)OSU6162 is consistent with dopamine hyperactivity in psychosis.

Assessing cocaine addiction vulnerability and neurobiological correlates within the nigrostriatal pathway using a novel model of dopamine D2 autoreceptor sensitivity

TLDR
It is found that rats with a high D2 autoreceptor sensitivity (PreHD2) are more sensitive to both the rewarding and psychomotor stimulating effects of cocaine than rats with A2A and B receptors.
...

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