About Dopamine

Psychosis and antipsychotic drugs[edit]

Main article: Psychosis

Psychiatrists in the early 1950s discovered that a class of drugs known as typical antipsychotics (also known as major tranquilizers), were often effective at reducing the psychoticsymptoms of schizophrenia.^[90] The introduction of the first widely used antipsychotic, chlorpromazine (Thorazine), in the 1950s, led to the release of many patients with schizophrenia from institutions in the years that followed.^[90] By the 1970s researchers understood that these typical antipsychotics worked as antagonists on the D2 receptors.^[90][91] This realization led to the so-called dopamine hypothesis of schizophrenia, which postulates that schizophrenia is largely caused, by hyperactivity of brain dopamine systems.^[92] The dopamine hypothesis drew additional support from the observation that psychotic symptoms were often intensified by dopamine-enhancing stimulants such as methamphetamine, and that these drugs could also produce psychosis in healthy people if taken in large enough doses.^[92] In the following decades other atypical antipsychotics that had fewer serious side effects were developed.^[90] Many of these newer drugs do not act directly on dopamine receptors, but instead produce alterations in dopamine activity indirectly.^[93] These drugs were also used to treat other psychoses.^[90] Antipsychotic drugs have a broadly suppressive effect on most types of active behavior, and particularly reduce the delusional and agitated behavior characteristic of overt psychosis.^[91] There remains substantial dispute, however, about how much of an improvement the patient experiences on these drugs.^[94]

Later observations, however, have caused the dopamine hypothesis to lose popularity, at least in its simple original form.^[92] For one thing, patients with schizophrenia do not typically show measurably increased levels of brain dopamine activity.^[92] Also, other dissociative drugs, notably ketamine and phencyclidine that act on glutamate NMDA receptors (and not on dopamine receptors) can produce psychotic symptoms.^[92] Perhaps most importantly, those drugs that do reduce dopamine activity are a very imperfect treatment for schizophrenia: they only reduce a subset of symptoms, while producing severe short-term and long-term side effects.^[95] Even so, many psychiatrists and neuroscientists continue to believe that schizophrenia involves some sort of dopamine system dysfunction.^[90] As the "dopamine hypothesis" has evolved over time, however, the sorts of dysfunctions it postulates have tended to become increasingly subtle and complex.^[90]

However, the widespread use of antipsychotic drugs has long been controversial.^[94] There are several reasons for this. First, antipsychotic drugs are perceived as very aversive by people who have to take them, because they produce a general dullness of thought and suppress the ability to experience pleasure.^[96] Second, it is difficult to show that they act specifically against psychotic behaviors rather than merely suppressing all types of active behavior.^[94] Third, they can produce a range of serious side effects, including weight gain, diabetes, fatigue, sexual dysfunction, hormonal changes, and a type of serious movement disorder known as tardive dyskinesia.^[95]Some of these side effects may continue long after the cessation of drug use, or even permanently.^[95]