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ISSN: 1935-1232 (P)

ISSN: 1941-2010 (E)

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Abstract

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

Author(s): Philip Seeman

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 supersensitivity is known to be a feature of schizophrenia and related psychoses, and because antipsychotics have a dopamine-blocking action, we examined proposed animal models of psychosis and their dopaminergic abnormalities. Results: All the animal models reveal elevations in D2High (D2 receptors with functional high-affinity for dopamine). The models reviewed include lesions, sensitization by drugs (amphetamine, phencyclidine, cocaine, corticosterone), birth injury, social isolation, and gene deletions in pathways for NMDA, dopamine, GABA, acetylcholine, and norepinephrine. Conclusion: Multiple abnormal pathways converge to a final common pathway of dopamine supersensitivity and elevated D2High dopamine receptors, perhaps responsible for clinical psychosis and amenable to antipsychotic treatment. Measurement of D2High in humans has not yet been clearly achieved, but will, in time, assist in the diagnosis and treatment of psychosis.