CHEMISTRY OF THE BRAIN: MOLECULES, MOOD, AND MENTAL ILLNESS - Chemistry: Notable Research and Discoveries - page 92

schizophrenia. Investigations into the drug's activity showed that this drug
binds to and blocks a certain type of dopamine receptor in the brain.
Receptors are proteins usually embedded in the cell's membrane.
A neurotransmitter such as dopamine docks at its receptor, activat-
ing it and initiating some kind of response in the postsynaptic cell. The
response depends on the type of receptor, and there are a number of
different ones for most neurotransmitters. Researchers have found five
dopamine receptors; the one affected by chlorpromazine and similar
drugs is known as D 2 . These drugs prevent dopamine from activating
the D 2 receptor.
Although measuring brain chemicals is difficult, several tech-
niques aid investigations of receptor function. One technique, known
as autoradiography, uses radioactive versions of neurotransmitters (or
other such molecules that bind receptors). Atoms of any given element
have the same number of protons in the nucleus, but some of these
atoms may vary in the number of neutrons and are known as isotopes
of the element. Some isotopes are stable, but some are not, decaying
and emitting radiation (radioactivity). For example, hydrogen-1 is a
stable isotope of hydrogen—the number indicates the number of pro-
tons and neutrons in the nucleus (one proton in this case). Hydrogen-3,
also known as tritium, has one proton and two neutrons, and unlike
hydrogen-1, tritium is radioactive. Detectors such as Geiger counters
are sensitive to the emitted radiation, as are certain chemical films.
Neurotransmitters in the body are not normally made of radioactive
atoms. Researchers make radioactive versions by adding radioactive at-
oms to the solution in which chemical reactions produce the molecule.
For example, hydrogen-3 can be incorporated into parts of a dopamine
molecule instead of hydrogen-1. Brain tissue can be cut into thin slices,
exposed to radioactive dopamine (or other radioactive molecules), and
then examined for radioactive traces, indicating receptors to which do-
pamine has attached. These procedures are known as autoradiography.
In 1976, Ian Creese, David R. Burt, and Solomon H. Snyder of Johns
Hopkins University in Baltimore, Maryland, reported that the most ef-
fective schizophrenia medications are the ones that have the strongest
affinity for dopamine receptors. Researchers also discovered drugs that
increased the amount of dopamine inadvertently caused schizophrenic
symptoms in patients. These findings led to the dopamine hypothesis of
schizophrenia—too much dopamine causes schizophrenia.