Researchers Discover Function for Brain's Marijuana-Like Compound
Researchers, funded in part by the National Institute on Drug Abuse (NIDA) of
the National Institutes of Health, have discovered a function for a natural
compound in the brain that is chemically similar to the active ingredient in
marijuana. This finding may lead to the development of new medications for
treating a wide variety of disorders.
Scientists have known since 1992 that the brain contains a compound that binds
to the same sites in the brain as delta-9-tetrahydrocannabinol (THC), the
active ingredient in marijuana. Evidence accumulated that this compound called
anandamide, inhibited movement when administered to laboratory animals. Now,
researchers at the University of California at Irvine; The Scripps Research
Institute in La Jolla, California; and Universidad Complutense in Spain; have
determined that anandamide inhibits movement by counteracting another brain
chemical called dopamine.
"This study of anandamide function in the brain is an example of how research
on drug abuse can lead to possible treatments for seemingly unrelated
diseases," says NIDA Director Dr. Alan I. Leshner. "Abnormalities in the
dopamine system in the brain are thought to play a major role in several
neurological and psychiatric disorders, as well as in drug addiction, so new
medications that can counteract these abnormalities might prove useful in
treating more than one disease."
The Scripps' researchers postulate that "anandamide and dopamine act in
opposite ways to control movements in an area of the brain called the dorsal
striatum." Dr. Andrea Giuffrida of the University of California at Irvine
explains that, "Dopamine stimulates movements by acting in this area, and
anandamide normally inhibits this action of dopamine."
Determining that anandamide can counteract dopamine may prove useful in the
development of medications for treating diseases that seem to involve dopamine
inbalances in the brain, suggests Dr. Giuffrida. Some diseases may be caused by
too much dopamine in certain brain regions, or perhaps hypersensitivity of
brain sites targeted by dopamine. These diseases include schizophrenia and
Gilles de la Tourette syndrome, which is characterized by facial tics,
repeating of words and phrases, and uncontrollable shouting of obscenities.
these diseases, medications that mimic anandamide might reduce symptoms by
dampening dopamine overactivity.
On the other hand, medications that block anandamide action in the brain may
prove useful in diseases that seem to involve too little dopamine in certain
brain regions or hyposensitivity of dopamine targets, he says. These diseases
include drug addiction and Parkinson's disease, a movement disorder.
In the study, Dr. Giuffrida and his colleagues first determined that
stimulating the nerve cells in the dorsal striatum, which is involved in
movement control, caused the nerve cells to release anandamide. This indicated
that anandamide, like dopamine, is one of the messenger chemicals that nerve
cells in the brain use for communicating with each other, according to the
The investigators then administered a dopamine-like drug called quinpirole into
the dorsal striatum, which caused the anandamide level in this area to jump
eightfold. This indicated that dopamine stimulates nerve cells in the dorsal
striatum that release anandamide.
Finally, the researchers looked at the effects of a compound that blocks
anandamide function on movements induced by quinpirole. After an hour,
quinpirole by itself caused the rats to move around their cage more and engage
in activities, such as sniffing, with greater frequency. However, pretreating
the rats with the anandamide blocker caused the rats to move around the cage
and sniff even more than they did with just quinpirole. This indicated that, in
the dorsal striatum, anandamide ordinarily inhibits dopamine's stimulatory
effect on movements, says Dr. Giuffrida. Administering the anandamide blocker
removed this inhibitory control, thereby allowing the dopamine-mimicking drug,
quinpirole, to stimulate movement even more than usual.
This study will be published in the April issue of Nature Neuroscience.
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