Abstract
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse.
Highlights
The adverse effects of alcohol consumption cause enormous health, social and economic burdens in societies worldwide
deep-brain stimulation (DBS) of NAc shell (NAcs) significantly increased the expression of alcohol-deprivation effect (ADE) when compared with sham-stimulated rats (factor stimulation: F (1,23) = 4.5, P o0.05; Figure 1a)
Verifying the localizations of the tip of the stimulation electrodes within the NAcs of the DBS group and calculating the distance of each electrode tip to the desired target within the NAcs, we found that the mean individual alcohol intake correlated negatively with the distance of the electrode tip placement to the desired target within the NAcs (Figure 2)
Summary
The adverse effects of alcohol consumption cause enormous health, social and economic burdens in societies worldwide. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) integrated alcohol abuse and alcohol dependence into one single disorder referred to as alcohol-use disorder.[1] The behavioral characteristics of this disorder are compulsive alcohol use, craving and relapses that can be observed even years following abstinence. The mechanisms of action of currently approved pharmacotherapies include interfering with alcohol’s metabolism, leading to an aversive physiological reaction following alcohol intake (disulfiram), targeting the reward pathways in the brain in an attempt to reduce alcohol reward and craving for alcohol (naltrexone and nalmefene) and interfering with a hyperglutamatergic system in order to avoid relapses (acamprosate).[3,4] the overall effect size of these medications is moderate and high relapse rates are still observed, outlining the need for the development of new therapeutic strategies
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call