Dopamine supersensitivity correlates with D2^High states, implying many paths to psychosis

Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine β-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th^-/-, Dbh^Th/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2^High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2^High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2^High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.