Involvement of the rostral agranular insular cortex in nicotine self-administration in rats

Pushparaj, Abhiram; Kim, Aaron S.; Musiol, Martin; Trigo, J.M.; Foll, Bernard Le

doi:10.1016/j.bbr.2015.04.039

Cited by 48 publications

(34 citation statements)

References 57 publications

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“…Such a shift in the qualitative, but not quantitative, nature of insula-dependent interoceptive control over addictive behaviour is in agreement with evidence from recent pre-clinical studies showing that perturbations to AIC function following drug exposure led to decreased instrumental responding for drugs (Cosme et al 2015; Pushparaj et al 2015), whereas pre-training lesions exacerbated cocaine seeking (Pelloux et al 2013). A qualitative, rather than quantitative understanding of the alteration in insula function during the progression from the initial drug use to addiction may also help reconcile the seemingly contradictory observations in humans that craving and relapse are associated with increased and decreased activity of the insula, respectively (Luo et al 2013; Mackey and Paulus 2013; Naqvi and Bechara 2009; Sinha 2011; Stewart et al 2014).…”

Section: Discussionsupporting

confidence: 85%

“…In rodents, the AIC has been associated with, or shown to be causally involved in, appetitive conditioning (Li et al 2013; Wu et al 2014), decision-making (Cocker et al 2016), impulsivity and the associated vulnerability to develop compulsive behaviour (Belin-Rauscent et al 2015). Similarly, lesions or inactivations of the AIC influence nicotine intake, cocaine seeking and responsivity to cocaine-related cues (Cosme et al 2015; Pelloux et al 2013; Pushparaj et al 2015), suggesting a role for insula-mediated interoceptive mechanisms in the reinforcing and incentive properties of addictive drugs.…”

Section: Introductionmentioning

confidence: 99%

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Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula

et al. 2017

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RationaleIncreasing evidence suggests that the anterior insular cortex (AIC) plays a major role in cocaine addiction, being implicated in both impaired insight and associated decision-making and also craving and relapse. However, the nature of the involvement of the insula in the development and maintenance of cocaine addiction remains unknown, thereby limiting our understanding of its causal role in addiction. We therefore investigated whether pre- and post-training bilateral lesions of the AIC differentially influenced the development and the expression of the escalation of cocaine self-administration during extended access to the drug.MethodsIn a series of experiments, Sprague Dawley rats received bilateral excitotoxic lesions of the AIC either prior to, or after 3 weeks of training under 12-h extended self-administration conditions, which are known to promote a robust escalation of intake. We also investigated the influence of AIC lesions on anxiety, as measured in an elevated plus maze and sensitivity to conditioned stimuli (CS)- or drug-induced reinstatement of an extinguished instrumental response.ResultsWhereas, post-escalation lesions of the AIC, as anticipated, restored control over cocaine intake and prevented drug-induced reinstatement, pre-training lesions resulted in a facilitation of the development of loss of control with no influence over the acquisition of cocaine self-administration or anxiety.ConclusionsAIC lesions differentially affect the development and maintenance of the loss of control over cocaine intake, suggesting that the nature of the contribution of cocaine-associated interoceptive mechanisms changes over the course of escalation and may represent an important component of addiction.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula

et al. 2017

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“…Contrary to our hypothesis, BM-induced AI inactivation at the time of memory reconsolidation (i.e., immediately after brief re-exposure to the previously cocaine-paired context) failed to inhibit drug context-induced reinstatement of cocaine-seeking behavior approximately 72 h later (Fig 4b–e). Expanding upon earlier studies that demonstrate the role of the AI in explicit CS-induced reinstatement of cocaine-seeking and nicotine-seeking behaviors (Cosme et al 2015; Pushparaj et al 2015a), the present findings indicate that the AI mediates the expression of drug context-induced cocaine-seeking behavior as opposed to the long-term, reconsolidation-dependent maintenance of cocaine memories stablished in the reinstatement paradigm.…”

Section: Discussionsupporting

confidence: 78%

Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats

et al. 2017

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Rationale Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. Objectives The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine-memory reconsolidation. Methods Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in Experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol, BM) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e. non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in Experiment 2 received vehicle or BM into the AI after a 15-min re-exposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. Results BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine-memory reconsolidation. Conclusions These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

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“…Our data on the role of AIV in relapse after voluntary abstinence agrees with previous studies on the role of the anterior insular cortex in relapse to drug seeking in rat models. Thus, reversible inactivation of this brain region decreases cue-induced reinstatement of cocaine and nicotine seeking (Cosme et al, 2015; Pushparaj et al, 2015), and context-induced reinstatement of cocaine seeking (Arguello et al, 2017). Additionally, post-training lesions of the anterior insula decreased cocaine priming-induced reinstatement of cocaine seeking (Rotge et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management

Vènniro¹,

Caprioli

Zhang³

et al. 2017

Neuron

138

149

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Summary Despite decades of research on neurobiological mechanisms of psychostimulant addiction, the only effective treatment for many addicts is contingency management, a behavioral treatment that uses alternative non-drug rewards to maintain abstinence. However, when contingency management is discontinued, most addicts relapse to drug use. The brain mechanisms underlying relapse after cessation of contingency management are largely unknown, and until recently, an animal model of this human condition did not exist. Here we used a novel rat model in which the availability of a mutually exclusive palatable food maintains prolonged voluntary abstinence from intravenous methamphetamine self-administration to demonstrate that activation of monosynaptic glutamatergic projections from anterior insular cortex to central amygdala is critical to relapse after cessation of contingency management. We identified the anterior insular cortex-to-central amygdala projection as a new addiction- and motivation-related projection and a potential target for relapse prevention.

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Involvement of the rostral agranular insular cortex in nicotine self-administration in rats

Cited by 48 publications

References 57 publications

Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula

Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula

Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats

The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management

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