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Interest in the habenula has greatly increased in recent years. The habenula is a small brain structure located posterior to the thalamus and adjacent to the third ventricle. Despite its small size, the habenula can be divided into medial habenula (MHb) and lateral habenula (LHb) nuclei that are anatomically and transcriptionally distinct. The habenula receives inputs from the limbic system and basal ganglia primarily via the stria medullaris. The fasciculus retroflexus is the primary habenular output from the habenula to the midbrain and governs release of glutamate onto gabaergic cells in the rostromedial tegmental nucleus (RMTg) and onto the interpeduncular nucleus. The resulting GABA released from RMTg neurons inactivates dopaminergic cells in the ventral tegmental area/substantia nigra compacta. Through this process, the habenula controls dopamine levels in the striatum. Thus, the habenula plays a critical role in reward and reward-associated learning. The LHb also modulates serotonin levels and norepinephrine release, while the MHb modulates acetylcholine. The habenula is a critical crossroad that influences the brain's response to pain, stress, anxiety, sleep, and reward. Dysfunction of the habenula has been linked to depression, schizophrenia, and the effects of drugs of abuse. This review focuses on the possible relationships between the habenula and drug abuse.

Abnormal interhemispheric functional connectivity correlates with several neurologic and psychiatric conditions, including depression, obsessive-compulsive disorder, schizophrenia, and stroke. Abnormal interhemispheric functional connectivity also correlates with abuse of cannabis and cocaine. In the current report, we evaluated whether tobacco abuse (i.e., cigarette smoking) is associated with altered interhemispheric connectivity. To that end, we examined resting state functional connectivity (RSFC) using magnetic resonance imaging (MRI) in short term tobacco deprived and smoking as usual tobacco smokers, and in non-smoker controls. Additionally, we compared diffusion tensor imaging (DTI) in the same subjects to study differences in white matter. The data reveal a significant increase in interhemispheric functional connectivity in sated tobacco smokers when compared to controls. This difference was larger in frontal regions, and was positively correlated with the average number of cigarettes smoked per day. In addition, we found a negative correlation between the number of DTI streamlines in the genual corpus callosum and the number of cigarettes smoked per day. Taken together, our results implicate changes in interhemispheric functional and anatomical connectivity in current cigarette smokers.

Electronic cigarettes (e-cigarettes) are nicotine-delivery devices that are increasingly used, especially by young people. Because e-cigarettes lack many of the substances found in regular tobacco, they are often perceived as a safer smoking alternative, especially in high-risk situations such as pregnancy. However, studies suggest that it is exposure to nicotine that is most detrimental to prenatal development. The authors studied perceptions of tobacco and e-cigarette health risks using a multiple-choice survey. To study the perceived safety of e-cigarettes versus tobacco cigarettes, 184 modified Global Health Youth Surveys (WHO, http://www.who.int/tobacco/surveillance/gyts/en/ ) were completed electronically or on paper. Age range, smoking status, and perceptions about tobacco cigarettes and e-cigarettes were studied. The results verified that younger people use e-cigarettes more than older people. Tobacco cigarettes were perceived as more harmful than e-cigarettes to health in general, including lung cancer and pregnancy. Although more research is necessary, the authors postulate that the perception that e-cigarettes are safer during pregnancy may induce pregnant women to use these devices more freely. Given that nicotine is known to cause fetal harm, pregnant mothers who smoke e-cigarettes could cause even greater harm to the fetus because e-cigarettes are perceived as being safer than tobacco cigarettes. Until more data about the effects of nicotine during pregnancy are available, the authors advocate for labeling of e-cigarettes as potentially harmful, at least during pregnancy.