The Dopamine Hypothesis: The notion that dopamine may be involved in schizophrenia derives from the therapeutic usefulness of drugs that block certain dopamine receptors in treating the disorder. Indeed, because dopamine blockers are so often effective, it has been proposed that an over activity of dopamine neurotransmission in cortical and limbic areas of the brain may cause schizophrenia. Drugs with selectivity for the D4 dopamine receptor (such as clozapine or olanzapine) can be particularly effective, and so this receptor subtype may play a critical role; in fact, elevated levels of D4 receptor binding have been found post-autopsy in the brains of persons who had schizophrenia. Dopamine is further implicated by the fact that a schizophrenia-like psychosis can be induced by abusing amphetamines, which act on dopamine pathways.
The NMDA Receptor Hypothesis: NMDA receptors respond to the excitatory neurotransmitter glutamate, and are known to be important for normal memory and cognition. Because drugs affecting NMDA receptors (such as ketamine or phencyclidine (PCP)) can cause schizophrenia-like hallucinations and because neuroleptic drugs, including clozapine, can inhibit their occurrence, it has been suggested that NMDA receptor dysfunction may cause schizophrenia. Recent studies have shown therapeutic benefit from drugs acting on NMDA receptors, such as glycine and D-cycloserine.