Abstract
The ventral striatum/nucleus accumbens (NAcc) has been implicated in the craving for drugs and alcohol which is a major reason for relapse of addicted people. Craving might be induced by drug-related cues. This suggests that disruption of craving-related neural activity in the NAcc may significantly reduce craving in alcohol-dependent patients. Here we report on preliminary clinical and neurophysiological evidence in three male patients who were treated with high frequency deep brain stimulation of the NAcc bilaterally. All three had been alcohol-dependent for many years, unable to abstain from drinking, and had experienced repeated relapses prior to the stimulation. After the operation, craving was greatly reduced and all three patients were able to abstain from drinking for extended periods of time. Immediately after the operation but prior to connection of the stimulation electrodes to the stimulator, local field potentials were obtained from the externalized cables in two patients while they performed cognitive tasks addressing action monitoring and incentive salience of drug-related cues. LFPs in the action monitoring task provided further evidence for a role of the NAcc in goal-directed behaviors. Importantly, alcohol-related cue stimuli in the incentive salience task modulated LFPs even though these cues were presented outside of the attentional focus. This implies that cue-related craving involves the NAcc and is highly automatic.
Highlights
Addiction, in particular to alcohol, is among the ten leading causes of disability in the world, placing an enormous emotional, social, and financial burden on society
For alcohol as well as other drugs such www.frontiersin.org as cocaine, craving-induced relapse has been shown to be induced by stressful life events, environmental stimuli previously associated with drug taking, or re-exposure to the drug itself (Spealman et al, 1999; Goeders, 2002; Epstein et al, 2006; Schmidt et al, 2006)
In animal experiments making use of the reinstatement paradigm, which uses the administration of relatively low doses of a drug to reinstate drug-seeking behavior, it has been shown that the nucleus accumbens (NAcc) is an important locus for reinstatement of drug-seeking behavior (Bachtell et al, 2005; Schmidt et al, 2005; Anderson et al, 2006; Schmidt et al, 2006)
Summary
In particular to alcohol, is among the ten leading causes of disability in the world, placing an enormous emotional, social, and financial burden on society. The concept of “wanting” [used in quotes as, for example, by Berridge and Robinson (Berridge and Robinson, 2003; Robinson and Berridge, 2008)] has featured prominently in this regard It refers to an underlying implicit and objective motivation process, incentive salience, and can be dissociated from hedonic aspects of addiction (termed“liking”).“Wanting” but not “liking” can explain compulsive drug intake even in situations in which the addict does not expect to experience a positive affect. Much like the mechanisms involved in reward prediction in animals, NAcc dopamine release attributes “incentive salience” to drug-associated cues (Robinson and Berridge, 2008). This cueinduced dopamine release, is thought to mediate “wanting” of alcohol or other drugs of abuse. Alcohol-addicted patients with downregulated dopaminergic neurotransmission in the ventral striatum are at a higher risk for relapse (Dettling et al, 1995; Heinz et al, 1996; George et al, 1999)
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