Because unpleasant withdrawal symptoms fuel nicotine addiction's high relapse rate, targeting their underlying mechanisms with treatments may promote continued abstinence from the drug. In a new JNeurosci paper, Alexis Monical and Daniel McGehee, from the University of Chicago, explored a neural pathway for nicotine withdrawal symptoms stemming from the interpeduncular nucleus (IPN) to the laterodorsal tegmentum (LDTg).
The researchers previously found that high doses of nicotine interact with the IPN to cause unpleasant effects that reduce intake of the drug in mice. Other researchers have linked the IPN to nicotine withdrawal symptoms. This nucleus inhibits the LDTg, which is emerging as a brain region that supports reward processing.
In their new paper, Monical and McGehee looked at neural activity in the LDTg as mice interacted with new objects and discovered that mice going through nicotine withdrawal had weaker LDTg responses to these objects. The researchers predicted that nicotine withdrawal may trigger the inhibitory projection from the IPN to the LDTg. In support of this prediction, artificially inhibiting the pathway—thus increasing LDTg activity—reduced withdrawal symptoms and increased interactions with new objects.
The authors are excited to develop strategies for targeting this pathway to alleviate unpleasant symptoms and potentially promote continued abstinence from nicotine.
