scholarly journals Subthalamic low-frequency oscillations predict vulnerability to cocaine addiction

2021 ◽  
Vol 118 (14) ◽  
pp. e2024121118
Author(s):  
Mickael Degoulet ◽  
Alix Tiran-Cappello ◽  
Etienne Combrisson ◽  
Christelle Baunez ◽  
Yann Pelloux
Keyword(s):  
Low Frequency ◽  
Cocaine Addiction ◽  
Oscillatory Activity ◽  
Prevention Strategies ◽  
Core Component ◽  
Low Frequency Oscillations ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Stn Dbs ◽  
Deep Brain

Identifying vulnerable individuals before they transition to a compulsive pattern of drug seeking and taking is a key challenge in addiction to develop efficient prevention strategies. Oscillatory activity within the subthalamic nucleus (STN) has been associated with compulsive-related disorders. To study compulsive cocaine-seeking behavior, a core component of drug addiction, we have used a rat model in which cocaine seeking despite a foot-shock contingency only emerges in some vulnerable individuals having escalated their cocaine intake. We show that abnormal oscillatory activity within the alpha/theta and low-beta bands during the escalation of cocaine intake phase predicts the subsequent emergence of compulsive-like seeking behavior. In fact, mimicking STN pathological activity in noncompulsive rats during cocaine escalation turns them into compulsive ones. We also find that 30 Hz, but not 130 Hz, STN deep brain stimulation (DBS) reduces pathological cocaine seeking in compulsive individuals. Our results identify an early electrical signature of future compulsive-like cocaine-seeking behavior and further advocates the use of frequency-dependent STN DBS for the treatment of addiction.

scholarly journals Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

2018 ◽  
Author(s):  
Mickaël Degoulet ◽  
Alix Tiran-Cappello ◽  
Christelle Baunez ◽  
Yann Pelloux
Keyword(s):  
Subthalamic Nucleus ◽  
Low Frequency ◽  
Predictive Biomarker ◽  
Progressive Increase ◽  
Oscillatory Activity ◽  
Diagnostic Tools ◽  
Consumption Pattern ◽  
Cocaine Seeking ◽  
Potential Strategy ◽  
Stn Dbs

AbstractCocaine seeking despite a foot-shock contingency is used to model compulsive drug seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed that only ‘compulsive-like’ rats displayed a progressive increase in STN low frequency oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in ‘non-compulsive’ animals changed them into ‘compulsive’ ones. We have thus identified a predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction research is to identify vulnerable individuals before they transition to harmful drug consumption pattern, our results could lead to new diagnostic tools and prevention strategies.

scholarly journals The Effects of Levodopa and Deep Brain Stimulation on Subthalamic Local Field Low-Frequency Oscillations in Parkinson's Disease

Neurosignals ◽  
2013 ◽  
Vol 21 (1-2) ◽  
pp. 89-98 ◽  
Author(s):  
Gaia Giannicola ◽  
Manuela Rosa ◽  
Sara Marceglia ◽  
Emma Scelzo ◽  
Lorenzo Rossi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Local Field ◽  
Brain Stimulation ◽  
Low Frequency ◽  
Low Frequency Oscillations ◽  
Deep Brain

scholarly journals Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

2011 ◽  
Vol 105 (3) ◽  
pp. 1112-1121 ◽  
Author(s):  
Harrison C. Walker ◽  
Ray L. Watts ◽  
Christian J. Schrandt ◽  
He Huang ◽  
Stephanie L. Guthrie ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Parkinson Disease ◽  
Brain Stimulation ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Antidromic Activation ◽  
Local Inhibition ◽  
Frequency Stimulation ◽  
Stn Dbs ◽  
Deep Brain

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.

scholarly journals Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease

2017 ◽  
Vol 126 (2) ◽  
pp. 397-403 ◽  
Author(s):  
Abigail Belasen ◽  
Khizer Rizvi ◽  
Lucy E. Gee ◽  
Philip Yeung ◽  
Julia Prusik ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Deep Brain Stimulation ◽  
Low Frequency ◽  
Detection Thresholds ◽  
Pain Thresholds ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation ◽  
Mechanical Detection ◽  
Stn Dbs ◽  
Deep Brain

OBJECTIVE Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST). METHODS Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain. RESULTS In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032). CONCLUSIONS Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

scholarly journals Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Valéria de Carvalho Fagundes ◽  
Carlos R. M. Rieder ◽  
Aline Nunes da Cruz ◽  
Bárbara Costa Beber ◽  
Mirna Wetters Portuguez
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Subthalamic Nucleus ◽  
Brain Stimulation ◽  
High Frequency ◽  
Verbal Fluency ◽  
Low Frequency ◽  
Stn Dbs ◽  
Deep Brain

Introduction.Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD.Methods.Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed.Results.The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS.Conclusion.Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients.

scholarly journals Deep brain stimulation of the nucleus accumbens shell does not decrease cocaine self-administration in cocaine-dependent rats but increases GluR1/GluA1 in the central nucleus of the amygdala

2018 ◽  
Author(s):  
Jenni Kononoff ◽  
Philippe A. Melas ◽  
Johanna S. Qvist ◽  
Giordano de Guglielmo ◽  
Marsida Kallupi ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Brain Stimulation ◽  
High Frequency ◽  
Cocaine Addiction ◽  
Central Nucleus ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Deep Brain

AbstractBackgroundCocaine addiction is a major public health problem. Despite decades of intense research, no effective treatments are available. Both preclinical and clinical studies of drug addiction strongly suggest that the nucleus accumbens (NAcc) is a viable target for deep brain stimulation (DBS).ObjectiveAlthough previous studies have shown that DBS of the NAcc decreases cocaine seeking and reinstatement, the effects of DBS on cocaine intake in cocaine-dependent animals have not yet been investigated.MethodsRats were made cocaine-dependent by allowing them to self-administer cocaine in long-access sessions (6 h, 0.5 mg/kg/infusion). The effects of high-frequency DBS of the NAcc shell on cocaine intake was then studied. Furthermore, cocaine-induced locomotor activity, irritability-like behavior during cocaine abstinence and the levels of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits 1 and 2 (GluR1/GluA1 and GluR2/GluA2) after DBS were investigated.ResultsContrary to our expectations, DBS of the NAcc shell induced a slight increase in both cocaine self-administration and cocaine-induced locomotor activity. In addition, 18 h into cocaine withdrawal, we found that DBS decreased irritability-like behavior. We also found that DBS-induced a robust increase in both cytosolic and synaptosomal levels of GluR1, but not GluR2, specifically in the central nucleus of the amygdala but not in other brain regions.ConclusionsThese preclinical results with cocaine-dependent animals do not support high-frequency DBS of the NAcc shell as a therapeutic approach for the treatment of cocaine addiction in active cocaine users. However, the decrease in irritability-like behavior during cocaine abstinence, together with previous findings showing that DBS of the NAcc shell reduces the reinstatement of cocaine seeking in abstinent animals, warrants future investigations of DBS as a treatment for negative emotional states and craving during abstinence.HighlightsHigh-frequency DBS of the NAcc shell for the treatment of cocaine addiction is proposedDBS of the NAcc shell does not decrease cocaine intake in cocaine-dependent ratsDBS increases the level of GluR1 specifically in the central nucleus of the amygdala

scholarly journals Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice

2020 ◽  
Author(s):  
Judit Cabana-Domínguez ◽  
Elena Martín-García ◽  
Ana Gallego-Roman ◽  
Rafael Maldonado ◽  
Noèlia Fernàndez-Castillo ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Cocaine Addiction ◽  
Cocaine Exposure ◽  
Self Administration ◽  
Normal Behavior ◽  
Cocaine Seeking ◽  
Seeking Behavior

ABSTRACTBackground and PurposeCocaine addiction causes serious health problems and no effective treatment is available yet. We previously identified a genetic risk variant for cocaine addiction in the PLCB1 gene and found this gene upregulated in postmortem brains of cocaine abusers and in human dopaminergic neuron-like cells after an acute cocaine exposure. Here, we functionally tested the contribution of PLCB1 gene to cocaine addictive properties in mice.Experimental approachWe used heterozygous Plcb1 knockout mice (Plcb1+/-) and characterized their behavioral phenotype. Subsequently, mice were trained for operant conditioning and self-administered cocaine for 10 days. Plcb1+/- mice were assessed for cocaine motivation, followed by 26 days of extinction and finally evaluated for cue-induced reinstatement of cocaine seeking. Gene expression alterations after reinstatement were assessed in medial prefrontal cortex (mPFC) and hippocampus (HPC) by RNAseq.Key ResultsPlcb1+/- mice showed normal behavior, although they had increased anxiety and impaired short-term memory. Importantly, after cocaine self-administration and extinction, we found a reduction in the cue-induced reinstatement of cocaine-seeking behavior in Plcb1+/- mice. After reinstatement, we identified transcriptomic alterations in the medial prefrontal cortex of Plcb1+/- mice, mostly related to pathways relevant to addiction like the dopaminergic synapse and long-term potentiation.Conclusions and ImplicationsTo conclude, we found that heterozygous deletion of the Plcb1 gene decreases cue-induced reinstatement of cocaine seeking, pointing at PLCB1 as a possible therapeutic target for preventing relapse and treating cocaine addiction.

scholarly journals Zinc potentiates dopamine neurotransmission and cocaine seeking

2020 ◽  
Author(s):  
Juan L. Gomez ◽  
Jordi Bonaventura ◽  
Jacqueline Keighron ◽  
Kelsey M. Wright ◽  
Dondre L. Marable ◽  
...  
Keyword(s):  
Conditioned Place Preference ◽  
Mechanism Of Action ◽  
Cocaine Abuse ◽  
Cocaine Addiction ◽  
Locomotor Sensitization ◽  
Self Administration ◽  
Pharmacological Mechanism ◽  
Cocaine Seeking ◽  
Seeking Behavior

AbstractCocaine binds to the dopamine transporter (DAT) in the striatum to regulate cocaine reward and seeking behavior. Zinc (Zn2+) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that cocaine abuse in humans correlated with low postmortem striatal Zn2+ content. In mice, cocaine decreased striatal vesicular Zn2+ and increased striatal synaptic Zn2+ concentrations and Zn2+ uptake. Striatal synaptic Zn2+ increased cocaine’s in vivo potency at the DAT and was required for cocaine-induced DAT upregulation. Finally, genetic or dietary Zn2+ manipulations modulated cocaine locomotor sensitization, conditioned place preference, self-administration, and reinstatement. These findings reveal new insights into cocaine’s pharmacological mechanism of action and indicate that Zn2+ can serve as a critical environmentally derived regulator of human cocaine addiction.

scholarly journals Modulation of high frequency by low-frequency Oscillations in the basal ganglia

2017 ◽  
Author(s):  
D. Nouri ◽  
R. Ebrahimpour ◽  
A. Mirzaei
Keyword(s):  
Basal Ganglia ◽  
Network Model ◽  
Large Scale ◽  
Low Frequency ◽  
Neural Mechanisms ◽  
Oscillatory Activity ◽  
Beta Band ◽  
Low Frequency Oscillations ◽  
Delta Band ◽  
Frequency Modulations

AbstractModulation of beta band fioscillatory activity (15-30 Hz) by delta band oscillatory activity (1-3 Hz) in the cortico-basal ganglia loop is important for normal basal ganglia functions. However, the neural mechanisms underlying this modulation are poorly understood. To understand the mechanisms underlying such frequency modulations in the basal ganglia, we use large scale subthalamo-pallidal network model stimulated via a delta-frequency input signal. We show that inhibition of external Globus Pallidus (GPe) and excitation of the Subthalamic nucleus (STN) using the delta-band stimulation leads to the same delta-beta interactions in the network model as the experimental results observed in healthy basal ganglia. In addition, we show that pathological beta oscillations in the network model decorrelates the delta-beta link in the network model. In general, using our simulation results, we propose that striato-pallidal inhibition and cortico-subthalamic excitation are the potential sources of the delta-beta link observed in the intact basal ganglia.

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