The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

Joshi, Dhaval D.; Puaud, Mickaël; Fouyssac, Maxime; Belin, David; Everitt, Barry J.; Belin, David

doi:10.1111/ejn.14889

Cited by 12 publications

(7 citation statements)

References 90 publications

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“…Accordingly, the insula has been singled out as a possible key brain region that connects all the three commented systems. As we mentioned earlier, the anterior insular cortex could exert a crucial influence over the loss of control in several addictions, including for example heroine consumption and its associated relapse tendency (Joshi et al, 2020 ).…”

Section: Discussionmentioning

confidence: 94%

Neural cue-reactivity in pathological gambling as evidence for behavioral addiction: a systematic review

García-Castro¹,

Cancela²,

Cárdaba³

2022

Curr Psychol

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Increasing incidence of problem gambling has led to prioritizing the problem from the point of view of public health. Additionally, gambling disorder has been recently classified as a behavioral addiction, with implications for both its diagnosis and treatment. However, the shared neural substrate of addictions, to substances and behavioral, is still discussed. Thus, this systematic review aims to provide up-to-date knowledge from the past five years (2017–2022) concerning the neural correlates of gambling related stimuli (cue-reactivity) on the basis of a previous review (Brevers et al., Cognitive, Affective and Behavioral Neuroscience 18:718–729, 2019 ). A total of five studies were included in the review. Activation of brain areas related to memory, reward and executive functions could be the underlying mechanism of this behavioral addiction. Specifically, nucleus accumbens and striatum (ventral and dorsal), parahippocampal regions, the right amygdala and several prefrontal cortex regions have systematically been found more active in those subjects exposed to gambling-related cues. Also, the insula could play a pivotal role connecting these three systems in a highly integrated neural network with several implications for reward processing modulation, associative learning and top-down attentional regulation to improve saliency of addiction-related cues. These results are consistent with previous findings on other substance addictions, such as alcohol, tobacco, marijuana or cocaine. The study of neural reactivity to stimuli related to addiction could be useful as a biomarker of the severity of the disorder, the efficacy of the treatment, the risk of relapse, in addition to being an objective criterion to measure the effectiveness of prevention campaigns.

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Section: Discussionmentioning

confidence: 94%

Neural cue-reactivity in pathological gambling as evidence for behavioral addiction: a systematic review

García-Castro¹,

Cancela²,

Cárdaba³

2022

Curr Psychol

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“…Since previous studies suggest that most aIC neurons are glutamatergic ( 15 , 22 ), we speculate that glutamatergic neurons of aIC play a role in modulation of compulsive cocaine use. To test our speculation, we inhibited aIC glutamatergic neurons by expressing calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) promoter inhibitory DREADD via infusion of AAV-CaMKIIα-hM4D-mCherry into aIC ( Fig.…”

Section: Resultsmentioning

confidence: 80%

An orbitofrontal cortex–anterior insular cortex circuit gates compulsive cocaine use

et al. 2022

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Compulsive drug use, a cardinal symptom of drug addiction, is characterized by persistent substance use despite adverse consequences. However, little is known about the neural circuit mechanisms behind this behavior. Using a footshock-punished cocaine self-administration procedure, we found individual variability of rats in the process of drug addiction, and rats with compulsive cocaine use presented increased neural activity of the anterior insular cortex (aIC) compared with noncompulsive rats. Chemogenetic manipulating activity of aIC neurons, especially aIC glutamatergic neurons, bidirectionally regulated compulsive cocaine intake. Furthermore, the aIC received inputs from the orbitofrontal cortex (OFC), and the OFC-aIC circuit was enhanced in rats with compulsive cocaine use. Suppression of the OFC-aIC circuit switched rats from punishment resistance to sensitivity, while potentiation of this circuit increased compulsive cocaine use. In conclusion, our results found that aIC glutamatergic neurons and the OFC-aIC circuit gated the shift from controlled to compulsive cocaine use, which could serve as potential therapeutic targets for drug addiction.

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“…Functional neuroanatomical studies have demonstrated that the anterior insular cortex (AIC) mediates a number of behaviors including cognitive, emotional, integrative and social functions, including attention, decision-making, and incentive and risk assessment. In rodents, lesions of the AIC or pharmacological modulations of this region alter cocaine intake and cocaine-seeking behaviors ( Arguello et al, 2017 ), conditioned opiate reward and aversion ( Wu et al, 2014 ; Wang et al, 2016 ), heroin self-administration ( Joshi et al, 2020 ) and nicotine self-administration ( Scott and Hiroi, 2011 ), confirming its role in addiction-related behaviors. However, precise neuroanatomical studies examining circuits involving the AIC that mediate these behaviors, especially in regards to heroin seeking, are sparse.…”

Section: Introductionmentioning

confidence: 84%

Early Life Stress Promotes Heroin Seeking But Does Not Alter the Excitability of Insular Pyramidal Cells Targeting the Nucleus Accumbens

Leyrer‐Jackson

Overby

Nagy

et al. 2021

Front. Behav. Neurosci.

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A number of retrospective studies have demonstrated adverse childhood experiences are associated with increased vulnerability to substance use disorders, including opioid use disorders (OUDs). These adverse childhood experiences, also referred to as early life stress (ELS), can be modeled in laboratory animals by various paradigms including limited bedding and nesting (LBN) procedures. Studies using rodent models of ELS have been shown to recapitulate various aspects of OUDs, including relapse propensity and perseverance of drug-seeking behavior. In the current study, we utilized the LBN paradigm to explore potential effects on heroin self-administration, extinction, and relapse-like behaviors in male and female rats. We also utilized in vitro whole-cell electrophysiology to examine the effects of LBN and repeated heroin administration on the excitability of pyramidal neurons in the anterior insular cortex (AIC) projecting to the nucleus accumbens core (NAc), as recent studies suggest that this circuit may mediate various aspects of OUDs and may be compromised as a result of either ELS or OUDs. We observed that compared to control animals, rats exposed to LBN conditions during postnatal days 2–9 showed increased breakpoints for heroin self-administration under a progressive ratio schedule of reinforcement, impaired extinction of heroin-seeking behavior, and increased reinstatement of heroin-seeking behavior induced by heroin-associated cues. No effect of LBN rearing conditions were observed on the acquisition and maintenance of heroin self-administration, and no sex differences in heroin intake were observed. LBN and control reared animals showed no differences in the excitability of AIC-NAc pyramidal neurons, but animals treated with repeated heroin showed decreased excitability of these neurons through a significant increase in rheobase and reduction in action potentials induced by depolarizing currents. Together, these results suggest that ELS exposure produces exacerbations of heroin seeking behavior without parallel effects on AIC-NAc excitability, although heroin itself reduces the excitability of these neurons.

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The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

Cited by 12 publications

References 90 publications

Neural cue-reactivity in pathological gambling as evidence for behavioral addiction: a systematic review

Neural cue-reactivity in pathological gambling as evidence for behavioral addiction: a systematic review

An orbitofrontal cortex–anterior insular cortex circuit gates compulsive cocaine use

Early Life Stress Promotes Heroin Seeking But Does Not Alter the Excitability of Insular Pyramidal Cells Targeting the Nucleus Accumbens

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