Increased Compulsivity in Adulthood after Early Adolescence Immune Activation: Preclinical Evidence.

Ángeles Prados-Pardo,Elena Martín-González,Margarita Moreno,Pilar Flores,Santiago Mora

doi:10.3390/ijerph18094684

Ángeles Prados-Pardo, Elena Martín-González + Show 3 more

Open Access

https://doi.org/10.3390/ijerph18094684

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Abstract

Immune activation during early developmental stages has been proposed as a contributing factor in the pathogenesis of neuropsychiatric conditions such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and autism in both human and animal studies. However, its relationship with the vulnerability to inhibitory control deficit, which is a shared feature among those conditions, remains unclear. The present work studied whether postnatal immune activation during early adolescence, combined with exposure to early-life adverse events, could lead to adult vulnerability to impulsive and/or compulsive behaviors. Male Wistar rats were exposed to lipopolysaccharide (LPS) in early adolescence at postnatal day 26 (PND26). During peripuberal period, half of the animals were exposed to a mild stress protocol. In adulthood, behavioral assessment was performed with the aid of the sustained attentional 5-choice serial reaction time (5-CSRT) task, schedule-induced polydipsia (SIP), and open-field locomotor activity and novelty reactivity. Rats exposed to LPS showed more compulsive responses than their control counterparts on 5-CSRT task, although no differences were observed in SIP or locomotor responses. Our study contributes to the knowledge of the relationship between immune activation and inhibitory control deficit. Future studies should aim to disentangle how, and to what extent, immune activation impacts behavior, and to understand the role of early life mild stress.

Highlights

Inhibitory control is an executive function that mediates our behavior by attention and reasoning, enabling us to inhibit or control predominant responses under environmental demands [1]
LPS created a vulnerability to compulsive behavior, as assessed by the 5-choice serial reaction time (5-CSRT) task perseverative responses during adulthood
These differences disappeared under long ITI (LITI) and extinction, where all groups showed a similar behavioral pattern concerning compulsivity and impulsivity, as assessed by premature responses

Summary

Introduction

Inhibitory control is an executive function that mediates our behavior by attention and reasoning, enabling us to inhibit or control predominant responses under environmental demands [1]. Failures in this process result in inhibitory control deficit, whose two main manifestations are impulsivity and compulsivity [2,3]. Impulsivity involves performing actions or making decisions that might result in potentially negative consequences for the individual and lack an appropriate forethought [4]. Compulsivity can be defined as a perseveration of a response that is irresistible and inappropriate to the individual and unavoidable despite its negative consequences [8]. The implication of dopamine, serotonin and fronto-striatal circuitry on inhibitory control deficit has been extensively studied [2,5,9]; the potential factors underlying the vulnerability towards this condition have been less extensively studied

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