Functional Brain Imaging of Addiction
The habenula is a very small structure that is very hard to disceern in functional MRI.
- In monkeys, the habenula activates when expected reward is not received (Matsumoto and Hikosaka, Nature 2007). When the habenula activates, dopamine in the striatum decreases.
- In mice, inactivation of the habenula is sufficient to observe nicotine withdrawal signs in dependent mice (Salas et al, 2009). Nicotine works in the brain through nicotinic acetylcholine receptors (nAChR). We show that some of the nAChR subunits are necessary to observe many of the effects of nicotine including withdrawal (a2, a3, a5, b4, Salas et al, 2003, 2004,2010).
- In humans, genetic variants in the a3, a5 and b4 subunits modulate the risk of becoming addicted to tobacco (Thorgeirsson, Bierut, Amos). These subunits are expressed in the habenula.
We are currently studying habenular activation upon reward and disappointment in sated and abstinent smokers, and we are collecting DNA to study how those genetic variants that are important for smoking behavior affect habenular activity.