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Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

ABSTRACT: Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03?mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

SUBMITTER: Pushparaj A

PROVIDER: S-EPMC3572467 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

Pushparaj Abhiram A Hamani Clement C Yu Wilson W Shin Damian S DS Kang Bin B Nobrega José N JN Le Foll Bernard B

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20121115 4

Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nic ...[more]

PMID: 23249816

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Project description:The subjective and behavioral effects of intracranial electrical stimulation (iES) have been studied for decades, but there is a knowledge gap regarding the relationship between the magnitude of electric current and the type, intensity and valence of evoked subjective experiences. We report on rare iES data from 18 neurosurgical patients with implanted intracranial electrodes in the orbitofrontal cortex (OFC), the insula (INS) and the anterior portion of cingulate cortex (ACC). ACC stimulation elicited somatic and visceral sensations, whereas OFC stimulation predominantly elicited olfactory and gustatory responses, and INS stimulation elicited a mix of effects involving somatic and visceral sensations, olfaction and gustation. Further, we found striking evidence that the magnitude of electric current delivered intracranially correlated positively with the perceived intensity of subjective experience and the evoked emotional state, a relationship observed across all three regions. Finally, we observed that the majority of reported experiences were negatively valenced and unpleasant, especially those elicited by ACC stimulation. The present study provides novel case studies from the human brain confirming that these structures contribute causally to the creation of affective states and demonstrates a direct relationship between the magnitude of electrical stimulation of these structures and the qualia of elicited subjective experience. Summary: This study provides critical knowledge about the effect of electrical charge magnitude on the intensity of human subjective experiences and emotional states. We shed light on the fundamental relationship between the electrical (physical) state of cortical tissue and the modality and intensity of human (subjective) experience. As electroceutical interventions are increasingly employed to treat neurological and psychiatric disorders, these findings highlight the importance of electrical stimulation magnitude for eliciting specific changes in human subjective experience.

Project description:BackgroundNeuroinflammation is an important driver of acute and chronic pain states. Therefore, targeting molecular mediators of neuroinflammation may present an opportunity for developing novel pain therapies. In preclinical models of neuroinflammatory pain, calcitonin gene-related peptide (CGRP), substance P and high mobility group box 1 protein (HMGB1) are molecules synthesized and released by sensory neurons which activate inflammation and pain. High-frequency electrical nerve stimulation (HFES) has achieved clinical success as an analgesic modality, but the underlying mechanism is unknown. Here, we reasoned that HFES inhibits neuroinflammatory mediator release by sensory neurons to reduce pain.MethodsUtilizing in vitro and in vivo assays, we assessed the modulating effects of HFES on neuroinflammatory mediator release by activated sensory neurons. Dorsal root ganglia (DRG) neurons harvested from wildtype or transgenic mice expressing channelrhodopsin-2 (ChR2) were cultured on micro-electrode arrays, and effect of HFES on optogenetic- or capsaicin-induced neuroinflammatory mediator release was determined. Additionally, the effects of HFES on local neuroinflammatory mediator release and hyperalgesia was assessed in vivo using optogenetic paw stimulation and the neuropathic pain model of chronic constriction injury (CCI) of the sciatic nerve.ResultsLight- or capsaicin-evoked neuroinflammatory mediator release from cultured transgenic DRG sensory neurons was significantly reduced by concurrent HFES (10 kHz). In agreement with these findings, elevated levels of neuroinflammatory mediators were detected in the affected paw following optogenetic stimulation or CCI and were significantly attenuated using HFES (20.6 kHz for 10 min) delivered once daily for 3 days.ConclusionThese studies reveal a previously unidentified mechanism for the pain-modulating effect of HFES in the setting of acute and chronic nerve injury. The results support the mechanistic insight that HFES may reset sensory neurons into a less pro-inflammatory state via inhibiting the release of neuroinflammatory mediators resulting in reduced inflammation and pain.

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Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

Publications

Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

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