Differential Involvement of the Agranular vs Granular Insular Cortex in the Acquisition and Performance of Choice Behavior in a Rodent Gambling Task.

Abhiram Pushparaj,Aaron S Kim,Zafiris J Daskalakis,Bernard Le Foll,Catharine A Winstanley,Martin Zack,Martin Musiol,Abraham Zangen

doi:10.1038/npp.2015.133

Abstract

Substance-related and addictive disorders, in particular gambling disorder, are known to be associated with risky decision-making behavior. Several neuroimaging studies have identified the involvement of the insular cortex in decision-making under risk. However, the extent of this involvement remains unclear and the specific contributions of two distinct insular subregions, the rostral agranular (RAIC) and the caudal granular (CGIC), have yet to be examined. Animals were trained to perform a rat gambling task (rGT), in which subjects chose between four options that differed in the magnitude and probability of rewards and penalties. In order to address the roles of the RAIC and CGIC in established choice behavior, pharmacological inactivations of these two subregions via local infusions of GABA receptor agonists were performed following 30 rGT training sessions. The contribution made by the RAIC or CGIC to the acquisition of choice behavior was also determined by lesioning these areas before behavioral training. Inactivation of the RAIC, but not of the CGIC, shifted rats' preference toward options with greater reward frequency and lower punishment. Before rGT acquisition, lesions of the RAIC, but not the CGIC, likewise resulted in a higher preference for options with greater reward frequency and lower punishment, and this persisted throughout the 30 training sessions. Our results provide confirmation of the involvement of the RAIC in rGT choice behavior and suggest that the RAIC may mediate detrimental risky decision-making behavior, such as that associated with addiction and gambling disorder.

Highlights

Gambling disorder is classified as an addictive disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders-5, due to findings establishing its similarity to substance-use disorders in terms of clinical expression, brain origin, comorbidity, physiology, and treatment (APA, 2013)
The current study examines the involvement of two insular subregions, the RAIC and CGIC, in a rodent model of decision-making under risk, the rat gambling task, which is similar to the Iowa gambling task (IGT), a human model of decision-making under risk (Zeeb et al, 2009)
Owing to the reciprocal connectivity of the RAIC, but not the CGIC, with areas such as the basolateral amygdala (BLA) and orbitofrontal cortex (Shi and Cassell, 1998b; Vertes, 2004), previously determined to be involved in choice behavior on the rat gambling task (rGT) (Zeeb and Winstanley, 2011), we hypothesized that 2833 only the RAIC would be involved in both the acquisition and performance of the rGT

Summary

INTRODUCTION

Gambling disorder is classified as an addictive disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders-5, due to findings establishing its similarity to substance-use disorders in terms of clinical expression, brain origin, comorbidity, physiology, and treatment (APA, 2013). Only two studies have examined the insular cortex in a rodent model of decision-making under risk (Ishii et al, 2012; St Onge and Floresco, 2010), a recent study has demonstrated that a dopamine D1 antagonist infused into the RAIC promotes impulsive decision-making (Pattij et al, 2014). The current study examines the involvement of two insular subregions, the RAIC and CGIC, in a rodent model of decision-making under risk, the rat gambling task (rGT), which is similar to the Iowa gambling task (IGT), a human model of decision-making under risk (Zeeb et al, 2009). Owing to the reciprocal connectivity of the RAIC, but not the CGIC, with areas such as the BLA and orbitofrontal cortex (Shi and Cassell, 1998b; Vertes, 2004), previously determined to be involved in choice behavior on the rGT (Zeeb and Winstanley, 2011), we hypothesized that. 2833 only the RAIC would be involved in both the acquisition and performance of the rGT

MATERIALS AND METHODS

RESULTS

DISCUSSION