**Contributors**

documented like impaired motivation, attention and executive functions [55, 56], in addition to very low effectiveness over addictive behaviors. Recent data showed decreased prefrontal activity on fRMN in drug-abuse patients and increased compulsive behavior after DBS of the

High-frequency stimulation of the subthalamic nucleus (STN) in Parkinsonian patients is reported to induce primarily motor effects but also psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative and limbic anatomo-functional territories. The sensorimotor territory (posterolateral) is the target for PD, while the associative-limbic territory (anteromedial) is the target for OCD. STN-DBS has not yet been tested in addicts, but there are clinical observations in PD patients after STN-DBS, reporting craving for sweet food in some cases or decreased addictive behavior toward DAergic treatment [19–22]. To date, there is no report of STN-DBS effects on any form of addiction in OCD patients, but in these patients, the compulsive component of the disease is reduced by the stimulation [64]. STN-DBS may play a role in preventing the loss of control of drug intake in addicts. The interest on STN-DBS in the treatment of addiction is based on clinical reports and preclinical data obtained in rats subjected to either lesion or DBS of STN. The stimulation of this target is able to dissociate various rewards, decreasing the motivation for the drug without diminishing other forms of motivated behaviors. This ability is demonstrated in two original studies. The first study documented the opposite effect of STN-DBS on the motivation for cocaine and for the natural reward; the other study proved that the stimulation of this target reduces motivation for cocaine while increasing motivation for sucrose, emphasizing the potential beneficial effects of STN-DBS for the treatment of cocaine addiction [23, 65]. Moreover, it was demonstrated that lesions of STN decreased incentive motivation (seeking behavior) for cocaine while inducing the opposite effect (facilitating incentive motivation) for food [23, 65–68]. This result suggests that STN-DBS may not be appropriate for all forms of addiction, but this remains to be investigated in other models of alcohol addiction. Therefore, STN represents a potentially effective target for the treatment of addiction that can decrease the desire for some drugs without influencing other motivated

Ethics in the history of psychosurgery has played a secondary role in experimentation due to the lack of effective medical therapy for mental disorders. The highest ethical standards for the use of DBS should be applied. The great suffering of patients and their poor quality of life, as well as the high social costs, are in favor of the use of this method in patients resistant to pharmacological therapy. Some fundamental ethical problems are mostly extendable to all clinical interventions as well as to neurostimulation procedures in neurological and psychiatric disorders. The reversibility of the method and the potential benefits are important ethical arguments for the use of DBS in addiction. On the other hand, DBS is not free of

lateral orbital cortex. The latter effect makes this procedure counterproductive [63].

**5.7. Nucleus subthalamicus (STN)**

6 Drug Addiction

behaviors.

**6. Conclusion**

The authors contributed equally to writing the manuscript.
