PMID:15716360

Citation	Seeman, P, Weinshenker, D, Quirion, R, Srivastava, LK, Bhardwaj, SK, Grandy, DK, Premont, RT, Sotnikova, TD, Boksa, P, El-Ghundi, M, O'dowd, BF, George, SR, Perreault, ML, Männistö, PT, Robinson, S, Palmiter, RD and Tallerico, T (2005) Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. Proc. Natl. Acad. Sci. U.S.A. 102:3513-8
Abstract	Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-, DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.
Links	PubMed PMC548961 Online version:10.1073/pnas.0409766102
Keywords	Animals; Catechol O-Methyltransferase/genetics; Catechol O-Methyltransferase/physiology; Corpus Striatum/physiopathology; Dopamine/physiology; Dopamine beta-Hydroxylase/genetics; Dopamine beta-Hydroxylase/physiology; Male; Phencyclidine/pharmacology; Psychotic Disorders/etiology; Quinpirole/pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2/genetics; Receptors, Dopamine D2/physiology; Receptors, Dopamine D4; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/physiology
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