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Unravelling the Neuroinflammatory Mechanisms Underlying the Effects of Social Defeat Stress on Use of Drugs of Abuse

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Neuroscience of Social Stress

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 54))

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Abstract

The immune system provides the first line of the organism’s defenses, working to maintain homeostasis against external threats and respond also to internal danger signals. There is much evidence to suggest that modifications of inflammatory parameters are related to vulnerability to develop mental illnesses, such as depression, autism, schizophrenia, and substance use disorders. In addition, not only are inflammatory parameters related to these disorders, but stress also induces the activation of the immune system, as recent preclinical research demonstrates. Social stress activates the immune response in the central nervous system through a number of mechanisms; for example, by promoting microglial stimulation, modifying peripheral and brain cytokine levels, and altering the blood brain barrier, which allows monocytes to traffic into the brain. In this chapter, we will first deal with the most important short- and long-term consequences of social defeat (SD) stress on the neuroinflammatory response. SD experiences (brief episodes of social confrontations during adolescence and adulthood) induce functional modifications in the brain, which are accompanied by an increase in proinflammatory markers. Most importantly, inflammatory mechanisms play a significant role in mediating the process of adaptation in the face of adversity (resilience vs susceptibility), allowing us to understand individual differences in stress responses. Secondly, we will address the role of the immune system in the vulnerability and enhanced sensitivity to drugs of abuse after social stress. We will explore in depth the effects seen in the inflammatory system in response to social stress and how they enhance the rewarding effects of drugs such as alcohol or cocaine. To conclude, we will consider pharmacological and environmental interventions that seek to influence the inflammatory response to social stress and diminish increased drug intake, as well as the translational potential and future directions of this exciting new field of research.

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Abbreviations

BBB:

Blood brain barrier

BLA:

Basolateral amygdala

CNS:

Central nervous system

CPP:

Conditioned place preference

CX3CL1:

Chemokine (C-X3-C motif) ligand 1

HPA:

Hypothalamic-pituitary-adrenal

HPC:

Hippocampus

IL:

Interleukin

LHb:

Lateral habenula

MDMA:

3,4-Methylenedioxymethamphetamine

mRNA:

Messenger RNA

NAcc:

Nucleus accumbens

PFC:

Prefrontal cortex

PrL:

Prelimbic cortex

SD:

Social defeat

STR:

Striatum

TLR:

Toll-like receptors

TLR4-KO:

TLR4 knockout

TNFa:

Tumor necrosis factor alpha

vHPC:

Ventral HPC

VWR:

Voluntary wheel running

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Acknowledgments

This work was supported by the Ministerio de Economía y Competitividad, Dirección General de Investigación, (PSI 2017-83023-R); Instituto de Salud Carlos III, Red de Trastornos Adictivos (RTA) (RD/16/0017/0007) and Unión Europea, Fondos FEDER “A way to build Europe.”

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Authors and Affiliations

  1. Department of Psychology and Sociology, University of Zaragoza, Teruel, Spain

    S. Montagud-Romero

  2. Department of Psychobiology, Facultad de Psicología, Universitat de Valencia, Valencia, Spain

    J. Miñarro & M. Rodríguez-Arias

  3. Red Temática de Investigación Cooperativa en Salud (RETICS-Trastornos Adictivos), Instituto de Salud Carlos III, MICINN and FEDER, Madrid, Spain

    J. Miñarro & M. Rodríguez-Arias

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Correspondence to M. Rodríguez-Arias .

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  1. Department of Psychology, Tufts University, Medford, MA, USA

    Klaus A. Miczek

  2. Department of Psychiatry, Yale Stress Center, Yale University School of Medicine, New Haven, CT, USA

    Rajita Sinha

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Montagud-Romero, S., Miñarro, J., Rodríguez-Arias, M. (2021). Unravelling the Neuroinflammatory Mechanisms Underlying the Effects of Social Defeat Stress on Use of Drugs of Abuse. In: Miczek, K.A., Sinha, R. (eds) Neuroscience of Social Stress. Current Topics in Behavioral Neurosciences, vol 54. Springer, Cham. https://doi.org/10.1007/7854_2021_260

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