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One of the key features of addiction is the escalated drug intake. The neural mechanisms involved in the transition to addiction remain to be elucidated. Since abnormal neuronal activity within the subthalamic nucleus (STN) stands as potential general neuromarker common to impulse control spectrum deficits, as observed in obsessive-compulsive disorders, the present study recorded and manipulated STN neuronal activity during the initial transition to addiction (i.e., escalation) and post-abstinence relapse (i.e., re-escalation) in rats with extended drug access. We found that low-frequency (theta and beta bands) neuronal oscillations in the STN increase with escalation of cocaine intake and that either lesion or high-frequency stimulation prevents the escalation of cocaine intake. STN-HFS also reduces re-escalation after prolonged, but not short, protracted abstinence, suggesting that STN-HFS is an effective prevention for relapse when baseline rates of self-administration have been re-established. Thus, STN dysfunctions may represent an underlying mechanism for cocaine addiction and therefore a promising target for the treatment of addiction.

Opioid addiction, including addiction to heroin, has markedly increased in the past decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction, particularly in individuals who are resistant to traditional therapies. Here we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction. STN HFS prevented the re-escalation of heroin intake after abstinence in rats with extended access to heroin, an animal model of compulsive heroin taking. STN HFS inhibited key brain regions, including the substantia nigra, entopeduncular nucleus, and nucleus accumbens shell measured using brain mapping analyses of immediate-early gene expression and produced a robust silencing of STN neurons as measured using whole-cell recording ex vivo. These results warrant further investigation to examine the therapeutic effects that STN HFS may have on relapse in humans with heroin addiction.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tins.2010.07.002 Byline: Paul Krack (1)(2), Marwan I. Hariz (3)(4), Christelle Baunez (5), Jorge Guridi (6)(7), Jose A. Obeso (6)(7) Abstract: Functional stereotaxy was introduced in the late 1940s to reduce the morbidity of lobotomy in psychiatric disease by using more focal lesions. The advent of neuroleptics led to a drastic decline in psychosurgery for several decades. Functional stereotactic neurosurgery has recently been revitalized, starting with treatment of Parkinson's disease, in which deep brain stimulation (DBS) facilitates reversible focal neuromodulation of altered basal ganglia circuits. DBS is now being extended to treatment of neuropsychiatric conditions such as Gilles de la Tourette syndrome, obsessive-compulsive disorder, depression and addiction. In this review, we discuss the concept that dysfunction of motor, limbic and associative cortico-basal ganglia-thalamocortical loops underlies these various disorders, which might now be amenable to DBS treatment. Author Affiliation: (1) Movement Disorders Unit, Department of Psychiatry and Neurology, University Hospital Grenoble, France (2) Grenoble Institute of Neuroscience, Inserm U836, Grenoble, France (3) Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK (4) Department of Clinical Neuroscience, University of Umea, Umea, Sweden (5) Laboratoire de Neurobiologie de la Cognition, Centre National de la Recherche Scientifique UMR6155, Aix-Marseille Universite, 13331 Marseille, France (6) Department of Neurology and Neurosurgery, Clinica Universitaria and Neuroscience Centre, Medical School, University of Navarra, Pamplona, Spain (7) Centro de Investigacion Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED), Centre for Applied Medical Research, Pamplona, Spain