Deep brain stimulation of the nucleus accumbens reduces ethanol consumption in rats

Division of Psychiatry, Boston University School of Medicine, 72 East Concord Street, R-620, Boston, MA 02118, USA.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 06/2009; 92(3):474-9. DOI: 10.1016/j.pbb.2009.01.017
Source: PubMed


Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to determine whether DBS delivered to either the shell or core of the NAcc would reduce ETOH intake in rats using a two-bottle choice limited access procedure. Long Evans rats were induced to drink a 10% ethanol solution using a saccharin fading procedure. Bipolar electrodes were implanted bilaterally into either the core or shell of the NAcc. During testing animals received DBS 5 min prior to and during a 30-minute test session in which both ETOH and water bottles were accessible. Current was delivered at amplitudes ranging from 0 to 150 microA. ETOH consumption was significantly reduced from baseline levels at the 150 microA current for both shell and core electrode placements. A significant current effect was not found for water consumption for either site. These results provide evidence that DBS delivered either to the nucleus accumbens core or shell subregions can significantly reduce ethanol intake in the rat.

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Available from: Domenic A Ciraulo,
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    • "In animal models of addiction, DBS of the nucleus accumbens prevented morphine-conditioned place preference [14], attenuated cocaine priming-induced reinstatement of drug seeking [15] [16], and decreased alcohol consumption [17]. However, although recent work indicates that accumbens DBS attenuated cue-induced reinstatement of heroin seeking [18], the influence of DBS on cue-induced reinstatement of cocaine seeking is unknown. "
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    ABSTRACT: Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254mg, i.v.) for 2h daily for 21 days, with each infusion of cocaine being paired with a cue light. After 21 days of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer. Copyright © 2014. Published by Elsevier B.V.
    Behavioural Brain Research 12/2014; 281. DOI:10.1016/j.bbr.2014.12.025 · 3.03 Impact Factor
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    • "Due to these contrasting actions of dopamine antagonists on dopamine dynamics during the time course of ethanol self-administration, it is difficult to relate specific patterns of dopamine transmission to behavioral changes. Furthermore, direct electrical stimulation of the nucleus accumbens in animal models, or deep-brain stimulation (DBS) of the accumbens of alcoholics, reduces ethanol drinking (Kuhn et al., 2007, 2011; Knapp et al., 2009; Muller et al., 2009; Henderson et al., 2010). However, it is possible that DBS, which induces the release of numerous neurotransmitters in the stimulated brain region, accomplishes its effect via non-dopaminergic mechanisms. "
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    ABSTRACT: There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors.
    Frontiers in Behavioral Neuroscience 11/2013; 7:173. DOI:10.3389/fnbeh.2013.00173 · 3.27 Impact Factor
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    • "As a result, deep brain stimulation (DBS) of the nucleus accumbens (NAc) is emerging as an effective treatment for reducing symptom severity in obsessive compulsive disorder (OCD) [2], [3], [4], [5], Tourette’s syndrome [6], [7], [8], [9], major depressive disorder [10], [11], [12], and alcoholism [13]. This practice is also supported by preclinical models, in which NAc stimulation reduces compulsive checking in quinpirole rat models of OCD [14], decreases alcohol consumption in alcohol preferring [15], [16] and attenuates re-instatement in cocaine-seeking [17], and morphine-preference in rats [18]. "
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    ABSTRACT: Deep Brain Stimulation (DBS) of the nucleus accumbens (NAc) has previously been investigated clinically for the treatment of several psychiatric conditions, including obsessive-compulsive disorder and treatment resistant depression. However, the mechanism underlying the therapeutic benefit of DBS, including the brain areas that are activated, remains largely unknown. Here, we utilized 3.0 T functional Magnetic Resonance Imaging (fMRI) changes in Blood Oxygenation Level-Dependent (BOLD) signal to test the hypothesis that NAc/internal capsule DBS results in global neural network activation in a large animal (porcine) model Animals (n = 10) were implanted in the NAc/internal capsule with DBS electrodes and received stimulation (1, 3, and 5 V, 130 Hz, and pulse widths of 100 and 500 µsec). BOLD signal changes were evaluated using a gradient echo-echo planar imaging (GRE-EPI) sequence in 3.0 T MRI. We used a normalized functional activation map for group analysis and applied general linear modeling across subjects (FDR<0.001). The anatomical location of the implanted DBS lead was confirmed with a CT scan We observed stimulation-evoked activation in the ipsilateral prefrontal cortex, insula, cingulate and bilateral parahippocampal region along with decrease in BOLD signal in the ipsilateral dorsal region of the thalamus. Furthermore, as the stimulation voltage increased from 3 V to 5 V, the region of BOLD signal modulation increased in insula, thalamus, and parahippocampal cortex and decreased in the cingulate and prefrontal cortex. We also demonstrated that right and left NAc/internal capsule stimulation modulates identical areas ipsilateral to the side of the stimulation Our results suggest that NAc/internal capsule DBS results in modulation of psychiatrically important brain areas notably the prefrontal cortex, cingulate, and insular cortex, which may underlie the therapeutic effect of NAc DBS in psychiatric disorders. Finally, our fMRI setup in the large animal may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS.
    PLoS ONE 02/2013; 8(2):e56640. DOI:10.1371/journal.pone.0056640 · 3.23 Impact Factor
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