The lateral habenula plays a key role in mediating and encoding aversive states.79 Numerous studies indicate that the habenula is one of the regions that control the decreases in dopamine neuron firing in the ventral tegmental area that are associated with failure to receive an expected reward.80,81 This hypothesis is also consistent with the finding that α5 nicotinic acetylcholine receptors in the habenula appear to modulate aversive responses to large doses of nicotine48 and, along with habenular α2 receptors, nicotine withdrawal (tables 1, 2, circuit 9).82
