Psychosis and dopamine High D2 receptors: Schizophrenia is a state of behavioural dopamine supersensitivity

Individuals with psychosis, particularly schizophrenia, are behaviorally supersensitive to dopamine-like drugs such as amphetamine or methylphenidate. Such supersensitivity may be associated with an increased pre-synaptic release of dopamine or a post-synaptic elevation of D2 receptors or of D2High receptors. The pre-synaptic release of dopamine is normal in remitted patients with schizophrenia. Brain imaging studies find that D2 receptors are only increased by 6% in anti-psychotic-naive schizophrenia patients. Therefore it is probable that the behavioural supersensitivity may arise from more D2High receptors in schizophrenia. After reducing endogenous dopamine, recent studies revealed an increase in apparent D2High receptors in schizophrenia. Animal models of psychosis, including dopamine-supersensitive animals pre-treated with amphetamine, marijuana or phencyclidine, or animals with gene knockouts in various neurotransmitter pathways, including those for glutamate receptors, have elevated levels of D2High receptors, consistent with behavioural dopamine supersensitivity in schizophrenia.