Safety and Feasibility of Nucleus Accumbens Surgery for Drug Addiction: A Systematic Review

Navarro, Paula Alejandra; Paranhos, Thiago; Lovo, Eduardo E; Oliveira‐Souza, Ricardo de; Gorgulho, Alessandra; Salles, Antônio De; López, William Omar Contreras

doi:10.1111/ner.13348

Cited by 19 publications

(14 citation statements)

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“…We next employed the rat intravenous cocaine self-administration (SA) assay – a robust SUD model that incorporates volitional drug use and relapse-associated behaviors, such as cue-reinstated drug seeking 54 . Using the pre-validated D1-Cre or D2-Cre BAC transgenic rats 55 , we infused Cre-dependent shNPAS4 or shScram viruses into the medial NAc core (NAcore) – a NAc subregion required for cue-reinstated cocaine seeking 4,5 . Following two weeks of daily, 2-hr cocaine SA sessions in D1- or D2-Cre rats (Figure 3E), we observed no significant differences produced by shNPAS4 NAcore on cocaine SA acquisition, number of drug infusions, operant discrimination of the active vs. inactive lever, or extinction of responding on the lever formerly paired with cocaine (Figure 3F,G and Figure S4A-F).…”

Section: Resultsmentioning

confidence: 99%

“…A fundamental neurobiological mechanism underlying relapse vulnerability in substance use disorder (SUD) is the formation of powerful associations between drug-induced euphoria and the diffuse and discrete cues in the drug-taking environment [1][2][3] . The nucleus accumbens (NAc) represents a key brain region that regulates motivated behavior, including relapse to drug seeking 4,5 . In animal models of SUD, the NAc plays an essential role in mediating relapse-like behaviors, and drug experiencedependent neuronal plasticity in this region is required for future drug-seeking behavior.…”

Section: Introductionmentioning

confidence: 99%

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NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

Hughes

Tsvetkov

Siemsen

et al. 2022

Preprint

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Use of addictive substances creates powerful drug-cue associations that often trigger relapse. Drug seeking is gated in the nucleus accumbens (NAc) by competing activation of D1 dopamine receptor-expressing medium spiny neurons (D1-MSNs) that promote, and D2 dopamine receptor-expressing neurons (D2-MSNs) that oppose, drug seeking. We show here that the ensemble of neurons in the NAc that induce the neuronal activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), is required for cocaine-context associations. In addition, NPAS4 functions within NAc D2-MSNs to govern the activation balance of NAc D1-MSNs and D2-MSNs necessary for drug-context memories and cue-induced cocaine, but not sucrose, seeking. NPAS4 regulates drug-cue associations and preponderant D1-MSN activation by influencing a program of gene expression that blocks cocaine-induced potentiation of prefrontal cortical excitatory drive onto D2-MSNs. Together our findings reveal that NPAS4 is a key player governing NAc MSN cell-type activation balance and promoting drug-cue associations and relapse vulnerability.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

Hughes

Tsvetkov

Siemsen

et al. 2022

Preprint

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“…In OCD patients treated with DBS of the nucleus accumbens, it was observed that those individuals who were heavy smokers or heavy drinkers, craving for nicotine, and alcohol decreased [74,75]. This led on to further so far unconclusive but "promising," trials aiming at treating alcohol as well as other drug addictions [76][77][78][79].…”

Section: Addiction/substance Abusementioning

confidence: 99%

Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s & Lozano’s Flashbacks

Hariz

Lees

Blomstedt

et al. 2022

Stereotact Funct Neurosurg

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Background: Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson’s disease, gabapentin for restless legs…). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures. Summary: James Parkinson’s observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson’s disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced tremor. Both the discoveries of the anterior limbic subthalamic nucleus as a DBS target for OCD and the medial forebrain bundle as a DBS target for depression occurred by chance. Hamani and Lozano observed memory flashbacks in a patient who was undergoing DBS for obesity, which led to the discovery of the fornix as a potential DBS target for Alzheimer’s disease. Key Messages: In the history of functional neurosurgery, serendipity and observations have resulted in discoveries of several procedures, brain targets for lesioning or DBS as well as new clinical surgical indications. In this era of neuromodulation, this technology should be exquisite in allowing potential serendipitous discoveries, provided that clinicians remain both observant and prepared.

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“…An alleged benefit of neuromodulation is that it is potentially reversible. This procedure does not require generating a permanent lesion in the neuronal circuitry similar to other procedures such as radiofrequency ablation, high-frequency ultrasound, or what is classically attributed as the mechanism of action of stereotactic radiosurgery (SRS) [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Radioneuromodulation by Dual-Target Irradiation in Pain Crisis From Trigeminal Neuralgia

Lovo¹,

Moreira²,

Barahona³

et al. 2022

Cureus

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BackgroundRadioneuromodulation (RNM) can explain the immediate pain relief experienced by a subgroup of patients after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). In this study, our main objective was to demonstrate that a minimum of a 50% reduction in TN pain can be achieved consistently in under 72 hours by targeting the affected nerve, the contralateral centromedian nucleus, and parafascicular complex in patients experimenting a prolonged refractory pain crisis. MethodologyWe treated eight patients experiencing severe TN pain crisis in whom percutaneous procedures had failed or were unwanted with SRS with an intention to procure pain relief in under 72 hours. The affected trigeminal nerve was targeted using a 4-mm collimator with an 80 to 90-Gy dose; an additional target was defined in the mesial portions of the thalamus and irradiated using the 4-mm collimator with a 120 to 140-Gy dose. ResultsThe median duration of TN was 60 months, the median duration of pain crisis was 10.7 weeks despite the best medical treatment, and the mean presenting visual analogue score (VAS) was 10 at the time of treatment. The median follow-up was 135 days (range, 65-210). Twenty-four hours after treatment, two (25%) patients had no pain (VAS 0), three (37.5%) had mild pain (VAS 1 to 3), and three (37.5%) had moderate pain (VAS 4 to 7). Forty-eight hours after treatment, all patients reported pain relief, seven (87.5%) reported >50%, and one (12.5%) patients reported 30% relief. The three-month median VAS score was 3 (range, 0 to 5). At the last follow-up, there were no adverse events to report. ConclusionsDual irradiation to the affected trigeminal nerve and contralateral mesial structures of the thalamus may provide fast pain relief for patients experiencing a prolonged pain crisis from TN, which veers away from the concept that the SRS pain relief effect is generally delayed and holds no place in the management of such patients. Although this is a small series with a limited follow-up duration, no adverse effects were noted.RNM can be defined as the capacity to alter neuronal activity through targeted delivery of a stimulus of radiation at a duration too brief to be explained by the development of a focal lesion. The immediate pain relief and its habitual oscillatory nature of lesser pain recurrence in most patients until enough time elapses for pain stabilization clinically demonstrates that the pain circuitry is altered and remains functional, thus accomplishing a neuromodulation effect even at the face of an apparent doses suspected to be ablative. Further research is needed to understand if this clinical effect is achieved with a suspected sub-ablative dose.

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Safety and Feasibility of Nucleus Accumbens Surgery for Drug Addiction: A Systematic Review

Cited by 19 publications

References 50 publications

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s & Lozano’s Flashbacks

Radioneuromodulation by Dual-Target Irradiation in Pain Crisis From Trigeminal Neuralgia

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Safety and Feasibility of Nucleus Accumbens Surgery for Drug Addiction: A Systematic Review

Cited by 19 publications

References 50 publications

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s &amp; Lozano’s Flashbacks

Radioneuromodulation by Dual-Target Irradiation in Pain Crisis From Trigeminal Neuralgia

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Product

Resources

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Serendipity and Observations in Functional Neurosurgery: From James Parkinson’s Stroke to Hamani’s & Lozano’s Flashbacks