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.
Bibliographical noteFunding Information:
This study was supported in part by a 2009 NARSAD Independent Investigator Award awarded to Dr Le Foll. Dr Hamani is a consultant and has received honoraria from St Jude Medical. Dr Le Foll has received grant and salary support from Pfizer and is a consultant for Richter Pharmaceuticals. AP, WY, DS, BK, and JN have no conflicts of interest to declare.
- deep brain stimulation