Contact: Beverly Jackson
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. In 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 scientists.
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.
NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute also carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on health effects of drugs of abuse and other topics can be ordered free of charge in English and Spanish, by calling NIDA Infofax at 1-888-NIH-NIDA (-644-6432) or 1-888-TTY-NIDA (-889-6432) for the deaf. These fact sheets and further information on NIDA research and other activities can be found on the NIDA home page at http://www.nida.nih.gov.