Summary: Tandospirone, a drug commonly used to treat anxiety related disorders, has been shown to reverse neurogenesis deficits caused by heavy alcohol use, researchers report.
Queensland University of Technology (QUT) researchers have identified a drug that could potentially help our brains reboot and reverse the damaging impacts of heavy alcohol consumption on regeneration of brain cells.
Their studies in adult mice show that two weeks of daily treatment with the drug tandospirone reversed the effects of 15 weeks of binge-like alcohol consumption on neurogenesis – the ability of the brain to grow and replace neurons (brain cells). The findings have been published in Scientific Reports.
- This is the first time tandospirone has be shown to reverse the deficit in brain neurogenesis induced by heavy alcohol consumption
- Tandospirone acts selectively on a serotonin receptor (5-HT1A)
- The researchers also showed in mice that the drug was effective in stopping anxiety-like behaviours associated with alcohol withdrawal, and this was accompanied by a significant decrease in binge-like alcohol intake
“This is a novel discovery that tandospirone can reverse the deficit in neurogenesis caused by alcohol,” said study leader neuroscientist Professor Selena Bartlett from QUT’s Institute of Health and Biomedical Innovation.
“We know that with heavy drinking you are inhibiting your ability to grow new neurons, brain cells. Alcohol is specifically very damaging for neurons.
“Other studies in mice have shown that tandospirone improves brain neurogenesis, but this is the first time it has been shown that it can totally reverse the neurogenic deficits induced by alcohol.
“This opens the way to look at if neurogenesis is associated with other substance-abuse deficits, such as in memory and learning, and whether this compound can reverse these.”
Professor Bartlett, who is based at the Translational Research Institute, said the discovery by study co-authors QUT postdoctoral research fellows Dr Arnauld Belmer and Dr Omkar Patkar came about serendipitously after research started in a different direction.
“It was surprising, and exciting,” Dr Belmer said.
“This drug is relatively new and available only in China and Japan. It is commonly used there and shown to be highly effective in treating general anxiety and well tolerated with limited adverse effects.”
Professor Bartlett said researchers are constantly looking at new treatment strategies for alcohol abuse and addiction, which is characterised by extended periods of heavy alcohol use, binges and abstinence, and anxiety and depression which contribute to relapse.
“This is not just another drug that shows promise in helping to reduce binge drinking,” she said.
“While it could possibly have that effect, it might be able to help reboot the brain and reverse the deficits the alcohol abuse causes – both the inhibition to the brain’s ability to regenerate, and the behavioural consequences that come from what alcohol is doing to the brain, like increases in anxiety and depression.”
Source: Justin Dupuis – QUT
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to QUT.
Video Source: Video credited to TheQUTube.
Original Research: Open access research in Scientific Reports.
5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol
Repeated episodes of binge-like alcohol consumption produce anxiety, depression and various deleterious effects including alterations in neurogenesis. While the involvement of the serotonin receptor 1 A (5-HT1A) in the regulation of anxiety-like behavior and neurogenesis is well documented, its contribution to alcohol withdrawal-induced anxiety and alcohol-induced deficits in neurogenesis is less documented. Using the Drinking-In-the-Dark (DID) paradigm to model chronic long-term (12 weeks) binge-like voluntary alcohol consumption in mice, we show that the selective partial activation of 5-HT1A receptors by tandospirone (3 mg/kg) prevents alcohol withdrawal-induced anxiety in a battery of behavioral tests (marble burying, elevated-plus-maze, open-field), which is accompanied by a robust decrease in binge-like ethanol intake (1 and 3 mg/kg). Furthermore, using triple immunolabelling of proliferation and neuronal differentiation markers, we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT1A partial agonist tandospirone (3 mg/kg/day). Together, our results confirm previous observations that 5-HT1A receptors play a pivotal role in alcohol drinking behavior and the associated emotional and neurogenic impairments, and suggest that 5-HT1A partial agonists represent a promising treatment strategy for alcohol abuse.