Dopamine supersensitivity correlates with D2Highstates, implying many paths to psychosis

Abstract

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.