Chronic Unilateral Stimulation of the Nucleus Accumbens at High or Low Frequencies Attenuates Relapse to Cocaine Seeking in an Animal Model

Hamilton, Jennifer J.; Lee, J.; Canales, Juan J.

doi:10.1016/j.brs.2014.09.018

Cited by 41 publications

(37 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we used a healthy rodent model, precluding behavioral tests of DBS efficacy, our evoked-fMRI results highlight strong parallels in circuit modulation by either moderate or high frequency stimulation of the NAc. Further, a recent preclinical study of NAc-DBS for cocaine addiction reported similar attenuation of reinstated drug-seeking behavior at 20 or 160 Hz, suggesting that some behavioral effects of NAc-DBS may also be frequency-insensitive17. The frequency sensitivity of symptom amelioration by NAc-DBS would be interesting to study in the clinical setting, particularly in light of the possibility of prolonging the battery life of DBS pulse generators using lower frequency stimulation protocols.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

Albaugh

Salzwedel

Berge

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action.

show abstract

Section: Discussionmentioning

confidence: 99%

“…This model was chosen based on its widespread use in preclinical studies of NAc-DBS151617181920. Electrical stimulation of the NAc strongly modulated prefrontal cortex and a diverse complement of subcortical limbic regions, including many areas not previously detected by DBS-fMRI.…”

mentioning

confidence: 99%

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

Albaugh

Salzwedel

Berge

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Briefly, the VS was bilaterally aimed with a concentric bipolar electrode with each polar end measuring 0.5 mm and 0.5 mm apart (NEX-100; Rhodes Medical Instruments). The DBS parameters used for high- and low frequency stimulation were similar to those used in humans and rodents (100–200 μA, 0.1 ms pulse duration, 130 Hz or 20 Hz) (29, 33, 40, 41). The stimulator (S88X) and constant current unit (SIC-C Isolation Unit; Grass Instruments) were connected to a commutator (Plastics One) through a cable that delivered the stimulation to the implanted electrodes.…”

Section: Methodsmentioning

confidence: 99%

“…As an alternative to high frequency DBS, low-frequency DBS (≤ 20 Hz) has been recently suggested as a treatment for addiction (26–28). In rats, low-frequency DBS of the VS attenuated cocaine relapse (29), and abolished cocaine sensitization when combined with pharmacological treatments (28). …”

Section: Introductionmentioning

confidence: 99%

Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum

Martínez-Rivera

Rodríguez-Romaguera

Lloret-Torres

et al. 2016

Biological Psychiatry

View full text Add to dashboard Cite

BACKGROUND Recent research in humans and rodents has explored the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VS) as a possible treatment for drug addiction. However, the optimum electrode placement and optimum DBS parameters have not been thoroughly studied. Here we varied stimulation sites and frequencies to determine whether DBS of the VS could facilitate the extinction of morphine-induced conditioned place preference in rats. Methods Rats were implanted with DBS electrodes in the dorsal or ventral subregions of the VS and trained to the morphine-CPP. Subsequently, rats received extinction sessions over 9 days, combined with 60 min of either high (130 Hz) or low (20 Hz) frequency DBS. To study circuit-wide activations after DBS of the VS, c-fos immunohistochemistry was performed in regions involved in the extinction of drug seeking behaviors. Results High frequency DBS of the dorsal-VS impaired both extinction training and extinction memory, whereas high frequency DBS of the ventral-VS had no effect. In contrast, low frequency DBS of the dorsal-VS strengthened extinction memory when tested 2 or 9 days after the cessation of stimulation. Both DBS frequencies increased c-fos expression in the infralimbic prefrontal cortex, but only low frequency DBS increased c-fos expression in the basal amygdala and the medial portion of the central amygdala. Conclusions Our results suggest that low frequency (rather than high frequency) DBS of the dorsal-VS strengthens extinction memory and may be a potential adjunct for extinction-based therapies for treatment-refractory opioid addicts.

show abstract

“…As alluded to, previous attempts to use glial derived neurotrophic growth factor - GDNF (Airavaara et al, 2011; Green-Sadan et al, 2003; Green-Sadan et al, 2005; Lu et al, 2009) and DBS (Hamilton et al, 2015; Rouaud et al, 2010; Vassoler et al, 2008; Vassoler et al, 2013) to mitigate cocaine reinstatement have been reported. In contrast to these methods, the use of RPEC grafts has the advantage that these grafts secrete L-dopa, the precursor for dopamine, and a variety of growth factors including GDNF, PEDF and a large number of anti-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking

Venkiteswaran

Alexander

Puhl

et al. 2016

Brain Research Bulletin

View full text Add to dashboard Cite

Chronic exposure to drugs and alcohol leads to damage to dopaminergic neurons and their projections in the ‘reward pathway’ that originate in the ventral tegmental area (VTA) and terminate in the nucleus accumbens (NAc). This damage is thought to contribute to the signature symptom of addiction: chronic relapse. In this study we show that bilateral transplants of human retinal pigment epithelial cells (RPECs), a cell mediated dopaminergic and trophic neuromodulator, into the medial shell of the NAc, rescue rats with a history of high rates of cocaine self-administration from drug-seeking when returned, after 2 weeks of abstinence, to the drug-associated chamber under extinction conditions (i.e., with no drug available). Excellent survival was noted for the transplant of RPECs in the shell and/or the core of the NAc bilaterally in all rats that showed behavioral recovery from cocaine seeking. Design based unbiased stereology of tyrosine hydroxylase (TH) positive cell bodies in the VTA showed better preservation (p<0.035) in transplanted animals compared to control animals. This experiment shows that RPEC grafts provide beneficial effects to prevent chronic relapse in drug addiction via its effects directly on the NAc and its neural network with the VTA.

show abstract

Chronic Unilateral Stimulation of the Nucleus Accumbens at High or Low Frequencies Attenuates Relapse to Cocaine Seeking in an Animal Model

Cited by 41 publications

References 50 publications

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum

Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking

Contact Info

Product

Resources

About