Chronic Distress in Male Mice Impairs Motivation Compromising Both Effort and Reward Processing With Altered Anterior Insular Cortex and Basolateral Amygdala Neural Activation.

Lidia Cabeza,Pierre-Yves Risold,Yvan Peterschmitt,Dominique Fellmann,Bahrie Ramadan,Emmanuel Haffen,Stephanie Cramoisy,Christophe Houdayer

doi:10.3389/fnbeh.2021.717701

Lidia Cabeza, Pierre-Yves Risold + Show 6 more

Open Access

https://doi.org/10.3389/fnbeh.2021.717701

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Abstract

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contributes to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward-processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from novelty suppressed feeding, operant effort-based choice, free feeding, and sucrose preference tasks) collectively show that behavioural initiation, effort allocation, and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlights CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how effort and reward processing contribute to adjust the motivational threshold triggering goal-directed behaviours in versatile environments.

Highlights

Motivation is defined as “a reason or reasons for acting or behaving in a particular way” (Husain and Roiser, 2018), and is often understood as a measure of the amount of energy or other resources that an individual is willing to invest in achieving a valued outcome (Berridge, 2004)
Impaired associative learning reported in psychiatric conditions (Horan et al, 2006; Der-Avakian and Markou, 2012; Griffiths et al, 2014) might result from abulia or anhedonia, but they are likely not the only contributors (Marin, 1990; Pizzagalli, 2014; Husain and Roiser, 2018).reward anticipation, which involves momentary motivational arousal in healthy conditions, effort valuation to obtain a reward, and motivation in a broad picture are, among others, processes involved in hedonic appreciation that may lead to variability in goal-directed behavioural outputs
Despite the fact that no significant correlations were found, including analyses of the caudal anterior insular cortex (aIC) (r = 0.4353, p = 0.18) and the ventral tegmental area (VTA) (r = 0.5094, p = 0.11), two positive trends were evidenced for BP scores and FosB-labelled cells densities in the bed nucleus of the stria terminalis (BNST) (r = 0.5621, p = 0.06; Figure 5L) and the basolateral amygdala (BLA) (r = 0.5087, p = 0.09; Figure 5M). These results, suggest a more intricate relationship between neural activation patterns and effort allocation in the progressive ratio (PR) task and point toward the influence of the BLA as a modulator of mice effort-based motivation in physiological conditions and upon chronic distress. The results of this experimental investigation show that chronic GC exposure has complex detrimental influences on motivational components subserving goal-directed behaviours and on appetitive and consummatory aspects involved in effort and reward valuation

Summary

Introduction

Motivation is defined as “a reason or reasons for acting or behaving in a particular way” (Husain and Roiser, 2018), and is often understood as a measure of the amount of energy or other resources that an individual is willing to invest in achieving a valued outcome (Berridge, 2004). Impaired associative learning reported in psychiatric conditions (Horan et al, 2006; Der-Avakian and Markou, 2012; Griffiths et al, 2014) might result from abulia (i.e., reduced ability to initiate an action) or anhedonia (i.e., reduced ability to feel pleasure or lack of reactivity to positive experience from reward), but they are likely not the only contributors (Marin, 1990; Pizzagalli, 2014; Husain and Roiser, 2018).reward anticipation, which involves momentary motivational arousal in healthy conditions, effort valuation to obtain a reward, and motivation in a broad picture are, among others, processes involved in hedonic appreciation that may lead to variability in goal-directed behavioural outputs

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