As we all know, cigarettes are highly addictive, and when you're trying to quit it's not unusual to feel a heightened level of anxiety. It's a problematic symptom that often causes people to give in to the craving and light up.
Now, in what could be a promising breakthrough to help people ditch the habit for good, scientists have identified the neural circuit and chemical signals that appear to cause anxiety during periods of nicotine withdrawal.
"Increased anxiety is a prominent nicotine withdrawal symptom that contributes to relapse in smokers attempting to quit," lead researcher and neuropsychiatrist, Andrew Tapper, from the University of Massachusetts in the US, said in a press release.
"We identified a novel circuit in the brain that becomes active during nicotine withdrawal, specifically increasing anxiety."
Tapper and researchers from the Scripps Research Institute in California have conducted experiments over several years examining a region of the brain called the interpeduncular nucleus, which has previously been linked to withdrawal symptoms.
They confirmed that this region is activated during nicotine withdrawal, and found that it appears to be responsible for feelings of increased anxiety.
Importantly, the team was able to differentiate between sub-regions of the interpeduncular nucleus, which were previously thought to be connected. What this means is that the feelings of anxiety are originating in a location separate from where other withdrawal symptoms originate, such as headaches, nausea and insomnia.
By examining the brains of mice, the researchers discovered that chemical signals dispatched from neurons in two other brain regions were converging in the interpeduncular nucleus, and that these signals were ultimately triggering anxiety-causing neurons housed there.
According to the researchers, some of these signals are coming from neurons in the ventral tegmental area(VTA), which is traditionally associated with the pleasure people feel from taking illicit drugs. The neurons in the VTA are activated through something called corticotropin releasing factor (CRF) - a hormone in the brain released in response to stress.
The other signals spurring anxiety are coming from the medial habenula via the release of a neurotransmitter called glutamate. These signals are made stronger by the presence of CRF, the researchers say.
The findings, which have been published in the journal Nature Communications, highlight the intricate mechanisms at play in the brain as it responds to nicotine withdrawal, and could help researchers develop new techniques to help smokers quit once and for all.
"Both of these inputs are important. We could alleviate anxiety during nicotine withdrawal by either preventing corticotropin releasing factor synthesis in the ventral tegmental area, or by silencing the medial habenula inputs into the interpeduncular nucleus," said Tapper.
The team was able to alleviate anxiety in mice by repressing the activity of these activated neurons, and believe this might also be possible in humans.
"There are already drugs that block the CRF receptor that contributes to activation of these anxiety-inducing neurons," Tapper noted. "These receptors have previously been linked to anxiety and depression, so our findings may also have implications for anxiety disorders in general."
The team is now trying to understand whether this circuitry is specific to nicotine, or whether it might also work with other addictive drugs, or with stress-induced anxiety.