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.

Damage to insula abolishes cognitive distortions during simulated gambling

“…Via a similar mechanism, insula activity has been linked to drug craving, such that smokers who suffered infarcts to the insula region quit smoking and described an abolition of the urge to smoke (42). Animal models have corroborated these effects of insula damage on drug self-administration, with lesions centered on posterior, granular insula (43,44). Therapeutic strategies to reduce insula responsivity, such as mindfulness-or meditationbased techniques (45,46) or GABAergic medications (47), may usefully augment cognitive therapy for psychological distortions in the treatment of problem gambling.…”

Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence

“…In both left and right INS, PSEs resulted in less deactivation than PNEs, an effect that was not observed for standard environments and proximal cues. The INS has been proposed as a critical substrate of tobacco use: smokers with insula damage exhibit increased likelihood of quitting smoking Naqvi et al, 2007); selfreported craving (Kuhn and Gallinat, 2011;Tang et al, 2012) and cessation outcomes (Janes et al, 2010) are correlated with insula reactivity to proximal smoking cues; and inactivation of insula decreases proximal cue-provoked nicotine seeking in rodents (Forget et al, 2010;Pushparaj et al, 2013). Less is known about the role of the insula in contextual drug effects; however, in a recent study, insula inactivation in rats led to disruption of amphetamine CPP (Contreras et al, 2012).…”

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

“…Procedures were similar to those previously reported [14,17]. All operant procedures were conducted in experimental chambers with two retractable levers located on a chamber wall (Med Associates, St. Albans, VT).…”

“…correlated to immediate smoking cessation easily achieved without craving or relapse. Though many human imaging studies followed [12], animal models have been critical to examine the effects of manipulating insular cortex function in various aspects of nicotine addiction [13][14][15][16][17].…”

“…Our previous studies [14,17], along with the work of others [15], have demonstrated that the caudal granular insular cortex (CGIC) plays an important role in rodent models of nicotine addiction. The CGIC integrates nociceptive [19] and unimodal viscerosensory [20] afferents from the thalamus along with those from the somatosensory cortex.…”