Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats

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Haaranen , M , Scuppa , G , Tambalo , S , Järvi , V , Bertozzi , S M , Armirotti , A , Sommer , W H , Bifone , A & Hyytiä , P 2020 , ' Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats ' , Translational Psychiatry , vol. 10 , no. 1 , 150 . https://doi.org/10.1038/s41398-020-0833-7

Title: Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats
Author: Haaranen, Mia; Scuppa, Giulia; Tambalo, Stefano; Järvi, Vilja; Bertozzi, Sine M.; Armirotti, Andrea; Sommer, Wolfgang H.; Bifone, Angelo; Hyytiä, Petri
Other contributor: University of Helsinki, Department of Pharmacology
University of Helsinki, Department of Pharmacology
University of Helsinki, Helsinki In Vivo Animal Imaging Platform (HAIP)



Date: 2020-05-18
Language: eng
Number of pages: 11
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
DOI: https://doi.org/10.1038/s41398-020-0833-7
URI: http://hdl.handle.net/10138/316286
Abstract: The anterior insular cortex plays a key role in the representation of interoceptive effects of drug and natural rewards and their integration with attention, executive function, and emotions, making it a potential target region for intervention to control appetitive behaviors. Here, we investigated the effects of chemogenetic stimulation or inhibition of the anterior insula on alcohol and sucrose consumption. Excitatory or inhibitory designer receptors (DREADDs) were expressed in the anterior insula of alcohol-preferring rats by means of adenovirus-mediated gene transfer. Rats had access to either alcohol or sucrose solution during intermittent sessions. To characterize the brain network recruited by chemogenetic insula stimulation we measured brain-wide activation patterns using pharmacological magnetic resonance imaging (phMRI) and c-Fos immunohistochemistry. Anterior insula stimulation by the excitatory Gq-DREADDs significantly attenuated both alcohol and sucrose consumption, whereas the inhibitory Gi-DREADDs had no effects. In contrast, anterior insula stimulation failed to alter locomotor activity or deprivation-induced water drinking. phMRI and c-Fos immunohistochemistry revealed downstream activation of the posterior insula and medial prefrontal cortex, as well as of the mediodorsal thalamus and amygdala. Our results show the critical role of the anterior insula in regulating reward-directed behavior and delineate an insula-centered functional network associated with the effects of insula stimulation. From a translational perspective, our data demonstrate the therapeutic potential of circuit-based interventions and suggest that potentiation of insula excitability with neuromodulatory methods, such as repetitive transcranial magnetic stimulation (rTMS), could be useful in the treatment of alcohol use disorders.
Subject: TRANSCRANIAL MAGNETIC STIMULATION
FUNCTIONAL CONNECTIVITY
PREFRONTAL CORTEX
SYNAPTIC PLASTICITY
VOLUNTARY ALCOHOL
CUE REACTIVITY
BRAIN
SYSTEMS
METAANALYSIS
INVOLVEMENT
3124 Neurology and psychiatry
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