[This is old news, but I want it here so I can find it easily. It helps to explain why it takes time to "reboot." The brain doesn't immediately "go back to normal" after extensive overstimulation. Delta FosB is one culprit. Here's another. If you feel "crazy" during withdrawal, you have good reason to!]
High Level of the Feel-Good Brain Chemical May Cause Depression
WebMD Health NewsJuly 28, 2005 -- A chemical in the brain normally associated with feelings of happiness and pleasure may also raise the risk of depression.
Researchers say they've found a new way in which prolonged exposure to the chemical messenger dopamine may play a role in depression as well as drug addiction. If confirmed by further studies, they say the discovery could lead to a new understanding of these complex disorders as well as better treatments.
Current antidepression treatments are mostly based on the deficiency or imbalance of the brain chemicals serotonin and norepinephrine, says researcher Li-Huei Tsai, a professor of pathology at Harvard Medical School, in a news release.
"This new study highlights the importance of the dopamine system, a less appreciated target in the current antidepression therapies," he says.
Short-term surges of dopamine are normally associated with feelings of pleasure. But abnormally high concentrations of the chemical messenger are linked to schizophrenia, attention deficit disorder, and other psychiatric disorders.
Two new studies looking at the association of dopamine, depression, and other psychiatric conditions appear in the current issue of Cell.
Dopamine and Depression
The studies show that certain receptors in the brain respond to dopamine in a previously unknown way that occurs over a period of hours rather than minutes or seconds. In this manner, researchers say the chemical may affect the brain indefinitely.
Receptors are proteins found on the surface of nerve cells that recognize and translate the signals from a chemical messenger to trigger a response by the cell.
In laboratory tests with mice, researchers found prolonged exposure to dopamine through this pathway inactivated a regulatory protein in the brain known as Akt and caused the mice to behave like they were depressed in response to stress.
In addition, inactivation of this protein caused a molecular chain of events that caused the mice to become desensitized to certain drugs.
Researchers say this type of prolonged exposure to dopamine may also help explain the impact of drug abuse on the brain. Most addictive drugs, such as cocaine and amphetamines, directly or indirectly raise dopamine levels, and the chemical plays a major role in drug-induced highs.
"This mechanism appears to be more important than those earlier described for prolonged stimulation by dopamine, as would be the case in those with psychiatric conditions," says researcher Marc Caron, PhD, professor of cell biology at Duke University, in a news release.
"The new pathway can now be evaluated for potential new inhibitors that might be better at controlling particular psychotic behaviors."