Elsevier

Behavioural Brain Research

Volume 270, 15 August 2014, Pages 118-124
Behavioural Brain Research

Research report
Dopaminergic modulation of impulsive decision making in the rat insular cortex

https://doi.org/10.1016/j.bbr.2014.05.010Get rights and content

Highlights

  • The agranular insular cortex is importantly involved in impulsive choice in rats.

  • Dopamine transmission in the insular cortex contributes to impulsive choice.

  • Infusion of a dopamine D1-like and not dopamine D2-like receptor antagonist in the agranular insular cortex modulates impulsive choice.

Abstract

Neuroimaging studies have implicated the insular cortex in cognitive processes including decision making. Nonetheless, little is known about the mechanisms by which the insula contributes to impulsive decision making. In this regard, the dopamine system is known to be importantly involved in decision making processes, including impulsive decision making. The aim of the current set of experiments was to further elucidate the importance of dopamine signaling in the agranular insular cortex in impulsive decision making. This compartment of the insular cortex is highly interconnected with brain areas such as the medial prefrontal cortex, amygdala and ventral striatum which are implicated in decision making processes. Male rats were trained in a delay-discounting task and upon stable baseline performance implanted with bilateral cannulae in the agranular insular cortex. Intracranial infusions of the dopamine D1 receptor antagonist SCH23390 and dopamine D2 receptor antagonist eticlopride revealed that particularly blocking dopamine D1 receptors centered on the insular cortex promoted impulsive decision making. Together, the present results demonstrate an important role of the agranular insular cortex in impulsive decision making and, more specifically, highlight the contribution of dopamine D1-like receptors.

Introduction

Intolerance to delay of gratification, oftentimes referred to as impulsive decision making, is a prominent feature of several psychiatric disorders such as attention-deficit/hyperactivity disorder [1] and substance use disorders [2]. Accumulating evidence originating from delay discounting paradigms has stressed the importance of dopamine transmission in these processes. In these paradigms, which have been developed for both humans and laboratory animals, impulsive decisions are operationalized as the preference for smaller-immediate over delayed-larger rewards when subjects are given the choice between both options [3].

For example, in healthy volunteers, treatment with the dopamine precursor l-dopa was found to promote choice for the sooner-smaller reward over larger-delayed reward [4]. In contrast, opposite findings have also been reported and increasing dopamine transmission in healthy volunteers via acute challenges with the psychostimulant and indirect dopamine agonist d-amphetamine [5] or the catechol-O-methyl transferase (COMT) inhibitor tolcapone [6] increased preference for the larger-delayed reward. These observations in humans are paralleled by preclinical studies in rats indicating that d-amphetamine promotes choice for the larger-delayed reward [7], [8], [9], whereas opposite effects of d-amphetamine on delay-discounting have also been found [10], [11], [12]. In addition, neurochemical and electrochemical studies in rats have indicated that performance in delay discounting paradigms is associated with increments in dopamine efflux in the brain [13], [14]. Together, the findings in humans and rats strongly point toward dopaminergic modulation of impulsive decision making, yet the direction seems variable and might perhaps be explained by, for instance, differences in trait impulsivity [15], altered dopaminergic tone through COMT polymorphisms [16], or interactions with other neurotransmitter systems such as serotonin [15], [17]. In terms of contributions of dopamine receptor subtypes, both dopamine D1-like and dopamine D2-like receptors have been implicated in impulsive decision making [7], [8].

Neuroimaging studies in humans have yielded further insights into the neural correlates of impulsive decision making and revealed increased activation patterns in the prefrontal cortex, including orbitofrontal cortex, insular cortex, as well as the ventral striatum when subjects engage in delay-discounting paradigms [18], [19], [20], [21], [22], [23]. Complementary to these neuroimaging data are the effects of excitotoxic lesions of similar brain regions in rats, including the ventral striatum and subregions of the orbitofrontal cortex, which were found to modulate impulsive decision making [24], [25], [26], [27], [28]. Based on such findings it has been postulated that the brain differentially codes smaller-immediate versus larger-delayed rewards, with areas such as the lateral orbitofrontal cortex and ventral striatum encoding immediate reward and more lateral prefrontal cortical areas including the insular cortex encoding delayed reward. Indeed, evidence from electrophysiological recordings in these aformentioned brain regions fits with this notion [29], [30], [31], [32], [33].

Functionally, the insular cortex has been postulated to play a key role in maintaining homeostasis by monitoring and integrating interoceptive visceral and somatic feelings and translating these to conscious emotional perceptions [34], [35]. Based on functional properties and relaying and processing information in a posterior to anterior manner, the insular cortex is divided into three main compartments, namely the posterior granular, dysgranular and anterior agranular insular cortex. In the rat brain, tract-tracing studies have demonstrated that each of these compartments has segregated reciprocal connections with other brain regions. The posterior granular and dysgranular insular cortices are primarily interconnected with visceral thalamic relay nuclei [36] and as such functionally implicated in monitoring and integrating interoceptive stimuli. The agranular insular cortex is largely interconnected with limbic structures including the medial prefrontal cortex, the amygdala and ventral striatum [36], [37]. Thus, the integration and translation of interoceptive stimuli to emotional feelings and behavioral actions seems to be coded in the agranular insular cortex. Moreover, the rat agranular insular cortex is highly innervated in terms of dopaminergic fibers [38] and the insular cortex (including the agranular insula) contains higher densities of dopamine D1-like receptors compared to dopamine D2-like receptors across species [39], [40], [41].

Taken together, the purpose of the present study was to examine the importance of dopamine signaling – and preferential involvement of dopamine D1-like over dopamine D2-like receptors – in the agranular insular cortex in impulsive decision making. To this aim, rats were trained in a delay discounting paradigm and subsequently received micro-infusions of the dopamine D1-like receptor antagonist SCH23390 or dopamine D2-like receptor antagonist eticlopride in the agranular insular cortex.

Section snippets

Subjects

Sixteen male Wistar rats were obtained from Harlan CPB (Horst, The Netherlands). At the start of the experiments animals weighed approximately 250 g, and were housed two per cage in macrolon cages (42.5 cm × 26.6 cm × 18.5 cm; length × width × height) under a reversed 12 h light/dark cycle (lights on at 7.00 p.m.) at controlled room temperature (21 ± 2 °C) and relative humidity of 60 ± 15%. Animals were maintained at approximately 90% of their free-feeding weight, starting one week prior to the beginning of the

Histological verification of cannulae placement

Following histological analyses, correct placement of the cannulae in the insular cortex was verified for all animals. In particular, infusion sites were located in the dorsal and ventral parts of the agranular insular cortex (Fig. 1). Two animals were excluded from all analyses because infusion sites were positioned outside the borders of the agranular insular cortex. Furthermore, one animal died during the surgical procedure and was therefore excluded from the analyses. Therefore, in total n = 

Discussion

To the best of our knowledge, this study is the first to demonstrate functional involvement of dopamine signaling in impulsive decision making in the rodent agranular insular cortex. We found that micro-infusions of the dopamine D1 receptor antagonist SCH23390 at a dose of 1 μg/side and not dopamine D2 receptor antagonist eticlopride into the agranular insular cortex in rats promoted choice for the smaller-immediate over larger-delayed reward in a delay-discounting task. As such the present data

Conflict of interest

The authors have no conflicts of interest to disclose.

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