Scientists shed light on how serotonin works

Scripps Research Institute scientists have shown for the first time that the neurotransmitter serotonin uses a specialised signaling pathway to mediate biological functions that are distinct from the signaling pathways used by hallucinogenic substances.
 
The new findings could have a profound effect on the development of new therapies for a number of disorders, including schizophrenia and depression.

The study was published in the October 6, 2010 issue of the Journal of Neuroscience.

Serotonin has tremendous influence over several brain functions, including the control of perception, cognition, sleep, appetite, pain, and mood and mediates these effects through interactions with receptors located throughout the central and peripheral nervous systems.

"Our study shows that while both serotonin and hallucinogens act at the serotonin 2A receptor, serotonin utilises a very specific pathway and its actions are independent of those produced by hallucinogens," said Laura Bohn, an associate professor on the Florida campus of The Scripps Research Institute.
 
"Future drug discovery efforts to identify lead compounds for treatment of depression may consider focusing upon those that only engage that pathway. This work may also lend insight into the mechanisms that underlie the hallucinations that occur in schizophrenia,"  Bohn added.

This may be particularly important, Bohn said, for the treatment of depression because traditional therapies, which focus on elevating serotonin levels, can sometimes produce serious side effects such as a serotonin syndrome. This syndrome is often accompanied by hallucinations, and is especially serious when antidepressant treatments such as selective serotonin reuptake inhibitors (SSRIs) are mixed with monoamine oxidase inhibitors (MAOIs).

The scientists' current study supports a long-standing hypothesis that hallucinations may arise from the metabolites formed from elevated serotonin levels. Since there is a difference in the way the two neurotransmitters signal, this may represent a means to preserve the effects of serotonin while preventing the adverse side effects caused by the metabolites.