Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis.
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,
Tallerico T.
Pharmacology Department, Medical Science Building, Room 4344, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8. philip.seeman@utoronto.ca
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.
PMID: 15716360 [PubMed - indexed for MEDLINE]
PMCID: PMC548961