UQ research uncovers how antidepressants actually work

Researchers at UQ's 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,” lead researcher Dr Dhanisha Jhaveri said.

“That suggests antidepressants must up-regulate neurogenesis in order for them to actually have any affect on behaviour.”

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

Dr Jhaveri said surprisingly, the class of antidepressants that increase levels of the neurotransmitter called serotonin - Prozac is a common example - fails to stimulate neurogenesis.

“Norepinephrine is basically binding directly onto the precursors which then initiate a signal which leads to the production of more neurons,” she said.

“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.

The researchers also improved their understanding of the mechanisms by which norepinephrine activated the precursors in the hippocampus and found the expression of beta3 adrenergic receptors is critical in mediating the effect.

Fellow researcher and team leader Professor Perry Bartlett said armed with this information, the team would 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,” Professor Bartlett said.

Dr Jhaveri said the findings would 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.

Media: Anna Bednarek, QBI Communications Manager (+61 7 3346 6414, a.bednarek@uq.edu.au).

Backgrounder:

Dr Dhanisha Jhaveri
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
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.

Queensland Brain Institute
The Queensland Brain Institute was established as a research institute of the University of Queensland in 2003. The Institute is now operating out of a new $63 million 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.