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

@article{Seeman2008AllPR,
  title={All Psychotic Roads Lead to Increased Dopamine D2High Receptors: A Perspective},
  author={Philip Seeman},
  journal={Clinical Schizophrenia \& Related Psychoses},
  year={2008},
  volume={1},
  pages={351-355}
}
  • P. Seeman
  • Published 24 January 2008
  • Psychology, Medicine
  • Clinical Schizophrenia & Related Psychoses
Objective: Brain dopamine supersensitivity is an established feature of schizophrenia. Animal models of schizophrenia also show dopamine supersensitivity, but surprisingly, no increase in dopamine D2 receptors. The objective is to determine the basis of dopamine supersensitivity in the animal models of schizophrenia, because this will be relevant to the clinical aspects. Method: This perspective reviews recent evidence from the animal and human literature. Because brain dopamine… 

Tables from this paper

Glutamate and dopamine components in schizophrenia.

  • P. Seeman
  • Psychology, Medicine
    Journal of psychiatry & neuroscience : JPN
  • 2009
TLDR
Assessing the basic and clinical findings shows that phencyclidine has DA D(2) agonist actions as well, and the clinical antipsychotic action of a glutamate agonist may depend on its ability to interfere with DA neurotransmission by its DA partial agonism.

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.

Do the Causal Paths to Psychosis Converge on D2High

TLDR
Clinical questions about why schizophrenia patients are supersensitive to dopamine-like stimulants are addressed by looking to animal models of psychosis, as limited as these models may be for schizophrenia itself.

d-serine and schizophrenia: an update

TLDR
Evidence suggests that research on the next generation of antipsychotic agents should include studies on increasing brain levels of d-serine or mimicking its action on the NMDA receptor.

Novel Targets for Development of Drugs for Treating Schizophrenia: Focus on Glycine, D-Serine and Nitric Oxide

TLDR
This review deals with three of those neurochemicals, namely glycine, D-serine and nitric oxide, and shows how an increased knowledge of them may be important in the future diagnosis and/or pharmacotherapy of schizophrenia.

Schizophrenia and the supersensitive synapse

TLDR
Supersensitivity of synapses compensates for and protects the brain from further injury, which leads to heightened neurotransmission, which is experienced subjectively as overstimulation, with subsequent attempts to psychologically adapt.

Amino Acids in Schizophrenia – Glycine, Serine and Arginine

TLDR
Behavioural studies in mutant mice in which D-serine levels are altered by manipulating catabolic or anabolic enzymes suggest that inhibitors of D-amino acid oxidase (DAO) may represent a useful future therapeutic approach to the treatment of schizophrenia.

The clinical and therapeutic potentials of dehydroepiandrosterone and pregnenolone in schizophrenia

Glycine Reuptake Inhibitors in the Treatment of Negative Symptoms of Schizophrenia

TLDR
A void in effective treatment options for negative symptoms persists and further research to improve psychiatric study design, discover clinical biomarkers and build on early successes of other potential pharmacologic molecules is required.

Hippocampal Pruning as a New Theory of Schizophrenia Etiopathogenesis

TLDR
The SKZ neurodevelopmental hypothesis is described, for the first time, starting from a single biological process, how alterations in pruning fine regulation and orchestration, strongly related with the evolutionary newest secreted proteins, may be of particular relevance in the hippocampus.

References

SHOWING 1-10 OF 18 REFERENCES

Psychosis pathways converge via D2High dopamine receptors

TLDR
The evidence suggests that there are multiple pathways that convergetoelevate the D2High state in brain regions and that this elevation may elicit psychosis.

Increased caudate dopamine D2 receptor availability as a genetic marker for schizophrenia.

TLDR
The results suggest that caudate dopamine dysregulation is also a trait phenomenon related to psychosis vulnerability, and provides a theoretical rationale for early pharmacologic intervention approaches using dopamine D(2) receptor blocking drugs.

Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia

TLDR
Findings confirm that alteration of DLPFC D1 receptor transmission is involved in working memory deficits presented by patients with schizophrenia.

“Breakthrough” Dopamine Supersensitivity during Ongoing Antipsychotic Treatment Leads to Treatment Failure over Time

TLDR
It is shown that during ongoing treatment with clinically relevant doses, haloperidol and olanzapine progressively lose their efficacy in suppressing amphetamine-induced locomotion and conditioned avoidance responding and is linked to an increase in D2 receptor number and sensitivity.

Provocative tests with psychostimulant drugs in schizophrenia

TLDR
The results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion and this biologic phenomenon may be clinically exploitable and should be investigated further.

Stimulant psychosis: systematic review

TLDR
Compliance with antipsychotic medication by someone with schizophrenia will not prevent a relapse or worsening of psychotic symptoms if stimulants are used, but low-dose antipsychotics treatment may be beneficial in stimulant users, to prevent sensitisation.

Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity.

TLDR
The authors suggest that DA-2 blockers, such as haloperidol or pimozide be employed as treatment of choice in PCP psychosis and tend to rule out a noradrenergic role.

The functional state of the dopamine receptor in the anterior pituitary is in the high affinity form.

TLDR
The data suggest that the high affinity state of the D2 dopamine receptor is the functional state which mediates the inhibition of PRL release.