Dopamine Hypothesis of Schizophrenia

Early research into the underlying molecular mechanisms of schizophrenia focused on the neurotransmitter dopamine and its activity within the mesolimbic pathway of the brain.

The association between dopamine and schizophrenia was made after observations that long term users of the illegal drug amphetamine, or people with amphetamine overdose, that did not have schizophrenia can experience periods of psychosis that were indistinguishable from those experienced by sufferers. Amphetamine produces its effect by blocking the reuptake of dopamine from the synapse (the microscopic space between two connecting neurons) into storage vesicles inside the neuron. These observations formed the basis of many years of research as it suggested that the symptoms of psychosis associated with schizophrenia might be the result of overactive dopaminergic signalling in the brain.

Research teams focused on developing ways of blocking the activation of the D2 dopamine receptor and after years of research the drugs chlorpromazine and haloperidol were identified as being D2 receptor antagonists reducing some of the positive symptoms of schizophrenia. Subsequent drugs have been added to form a group known as the typical antipsychotics. New evidence suggests that the mechanisms of schizophrenia are not only to do with dopamine signalling as new drugs, known as atypical antipsychotics, have been discovered that do not block the D2 receptor.