Deep brain stimulation for the treatment of addiction: basic and clinical studies and potential mechanisms of action

Abstract

Rationale: Deep brain stimulation (DBS) has achieved substantial success as a treatment for movement disorders such as Parkinson's disease. The therapeutic efficacy and relative lack of serious side effects resulted in the expansion of DBS into the treatment of many other diseases, including obsessive-compulsive disorder, Tourette's, and depression, among others. More recently, a limited number of basic and clinical studies indicated that DBS may also be useful in the treatment of various addictions.

Objectives: Here, we briefly summarize the history of DBS and review the basic and clinical studies focused on DBS and addiction. We also examine the potential mechanisms that may underlie the effects of DBS.

Results and conclusions: The available data indicate that DBS is a promising therapeutic modality for the treatment of addiction. Thus far, the nucleus accumbens and subthalamic nucleus are the most promising sites for DBS, reversing aspects of addiction. The mechanisms underlying DBS are complex and likely vary from region to region. Emerging evidence indicates that DBS of the nucleus accumbens produces its effects, at least in part, by antidromic activation of cortico-accumbal afferents that stimulate inhibitory medial prefrontal cortex interneurons via recurrent collaterals.

Figure 1

Cartoon depicting a mechanism whereby DBS of nucleus accumbens (NAc) influences neuronal activity in the medial prefrontal cortex (mPFC). It is proposed that DBS of the NAc (1) produces antidromic activation of cortico-accumbal afferents (2) that stimulates mPFC interneurons via recurrent collaterals (3). DBS-induced activation of mPFC GABAergic interneurons (neuron with black circle cell body), in turn, inhibits cortical pyramidal neurons (neuron with triangular cell body). Modified from McCracken and Grace, 2007.