Anxiety associated with smoking cessation is a common side effect of nicotine withdrawal. A new study may offer smokers a promising breakthrough as researchers have identified the brain circuits responsible for the anxiety.
“We identified a novel circuit in the brain that becomes active during nicotine withdrawal, specifically increasing anxiety,” said principal investigator Andrew Tapper, Ph.D. , associate professor of psychiatry at the University of Massachusetts Medical School (UMMS).
“Increased anxiety is a prominent nicotine withdrawal symptom that contributes to relapse in smokers attempting to quit.”
The study yielded several discoveries about interconnected brain mechanisms that induce anxiety during nicotine withdrawal, and possible ways to derail these mechanisms in order to treat, or even prevent the especially troublesome symptom.
Experiments leading to the multiple, related findings were conducted over several years by the laboratories at UMMS and The Scripps Research Institute of La Jolla, California.
The study is published online by Nature Communications.
Researchers believe the study’s main finding is that a brain region called the interpeduncular nucleus is activated and appears to cause anxiety during nicotine withdrawal. Apparently, the anxiety linked to withdrawal occurs in this distinct subregion of the brain, and not the area where physical nicotine withdrawal symptoms such as headaches, nausea, and insomnia originate.
This form of anxiety strongly affects mood and often blocks smokers’ attempts to quit. The newly discovered sub region offers a distinct target for dampening these affective symptoms of nicotine withdrawal.
Also newly identified is the fact that input from neurons in two other brain regions converge onto the interpeduncular nucleus to stimulate anxiety-provoking neurons. Even areas of the brain traditionally associated with the rewarding or pleasurable effects of abused drugs, activate neuron receptors that foster anxiety. Also surprising to researchers is that other neurons release glutamate, the major excitatory neurotransmitter in the brain.
Both of these inputs are important and we could alleviate anxiety during nicotine withdrawal by dampening the activity at either level, said Tapper.
Investigators were able to alleviate anxiety in mice by quieting the activity of those activated neurons, suggesting the same might be possible for humans.
“There are already drugs that block the 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.”
Next steps for this productive research collaboration will be expanding the scope of scientists’ understanding of the interactions between anxiety, stress, reward, and withdrawal from addictive substances.
“We’re now exploring whether the circuitry that we identified is involved in stress-induced anxiety in general, or specific to nicotine withdrawal-induced anxiety,” Tapper said.
“We’re also exploring if this circuitry is engaged with other drugs of abuse.”