All in the Mind - How antidepressants actually work

18 Feb 2010

Researchers at the Queensland Brain Institute have uncovered how antidepressants stimulate the brain to improve a person’s mood.

They have discovered the class of drugs that increase levels of a neurotransmitter known as ‘norepinephrine’ triggers neurogenesis (the growth of new neurons) in a brain region called the hippocampus.

“If you block hippocampus neurogenesis, antidepressants no longer work. That suggests antidepressants must up-regulate neurogenesis in order for them to actually have any affect on behaviour,” lead researcher Dr Dhanisha Jhaveri said.

However, the neuroscientists also found that not all antidepressants work in the same way.

Surprisingly, the class of antidepressants that increase levels of the neurotransmitter called serotonin (Prozac is a common example) fails to stimulate neurogenesis.

Dr Jhaveri explained: “Norepinephrine is basically binding directly onto the precursors which then initiate a signal which leads to the production of more neurons. Serotonin just doesn’t do that. Prozac doesn’t work by regulating the precursor activity – it may work outside that region, but it isn’t regulating the hippocampus directly. More research is needed to find out what serotonin actually does.”

Using rodent models the research, published today in the Journal of Neuroscience, established that selectively blocking the re-uptake of norepinephrine directly activated hippocampal stem cells thereby discovering a much larger pool of dormant precursors in the hippocampus than previously thought to exist.

Further, scientists improved their understanding of the mechanisms by which norepinephrine activated the precursors in the hippocampus and found that the expression of beta3 adrenergic receptors is critical in mediating the effect.

Armed with this information, the team will now be able to explore improved treatments for depression, as well as dementia.

“Since dementia - especially in the ageing population - appears to be related to a decrease in neurogenesis this discovery opens up exciting new ways to stimulate the production of new neurons to alleviate the devastating effects of dementia in our society,” said fellow researcher and team leader Professor Perry Bartlett.

The findings will also allow researchers to develop specific and more effective antidepressants.

“Depression is such a complex disorder, so we are going to test different behavioural outcomes to see whether the compounds that increase norepinephrine levels or stimulate beta3 adrenergic receptors work only for certain aspects of depression. We just don’t know yet but it may, for example, improve learning and memory, or reduce anxiety,” Dr Jhaveri said. 


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Notes to the Editor
Dr Dhanisha Jhaveri, a postdoctoral fellow and recipient of the human frontiers science programme long-term fellowship, has been working with Professor Perry Bartlett since 2003. She was awarded the Indian National Science Academy’s medal for young scientist of the year in 2003 for her doctoral thesis.

Professor Perry Bartlett is internationally renowned in the field of cellular and molecular neuroscience, a fact highlighted by his election as a Fellow of the Australian Academy and the awarding of a prestigious Australian Research Council Federation Fellowship in
2003. In 2002 he was appointed Foundation Chair in Molecular Neuroscience at The University of Queensland and the inaugural Director of the Queensland Brain Institute in 2003.

The Queensland Brain Institute (QBI) was established as a research institute of the University of Queensland in 2003. The Institute is now operating out of a new $63m state-of-the-art facility and houses 27 Principal Investigators with strong international reputations. QBI is one of the largest neuroscience institutes in the world dedicated to understanding the mechanisms underlying brain function.