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 D2^High 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 D2^High receptors in schizophrenia. After reducing endogenous dopamine, recent studies revealed an increase in apparent D2^High 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 D2^High receptors, consistent with behavioural dopamine supersensitivity in schizophrenia.