Nicotine is often thought of as a rewarding stimulus. But it also has aversive properties, and these different motivational effects seem to be mediated by circuits that include the ventral tegmental area (VTA). Laviolette et al. now take a step towards unravelling these circuits, by showing that lesions of the tegmental pedunculopontine nucleus (TPP) can cause a switch in the motivational effects of nicotine infusions into the VTA, from rewarding to aversive.

The TPP receives inputs — thought to be inhibitory and mediated by GABA (γ-aminobutyric acid) — from the VTA, and sends cholinergic projections back to the VTA. Previous studies have shown that the TPP is important for the rewarding effects of several drugs. In the new study, Laviolette et al. infused nicotine directly into the VTA of rats, where it produced a rewarding effect, measured by conditioned place preference. But when the TPP was lesioned bilaterally, the rewarding effect was blocked, and instead the rats showed a conditioned aversion for sites associated with nicotine infusion. TPP lesions did not block the induction of conditioned taste aversion by systemic nicotine administration — another measure of the aversive effects of nicotine.

So, it appears that the TPP is crucial for the rewarding effects of nicotine in the VTA, and that removal of the TPP reveals an aversive effect that is presumably mediated by a different circuit. The authors suggest that, whereas the aversive effects of nicotine are mediated by an ascending dopaminergic system, its rewarding effects are mediated by a non-dopaminergic pathway that includes the TPP.