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Neuroinflammatory Response in Reward-Associated Psychostimulants and Opioids: A Review

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Abstract

Substance abuse is one of the significant problems in social and public health worldwide. Vast numbers of evidence illustrate that motivational and reinforcing impacts of addictive drugs are primarily attributed to their ability to change dopamine signaling in the reward circuit. However, the roles of classic neurotransmitters, especially dopamine and neuromodulators, monoamines, and neuropeptides, in reinforcing characteristics of abused drugs have been extensively investigated. It has recently been revealed that central immune signaling includes cascades of chemokines and proinflammatory cytokines released by neurons and glia via downstream intracellular signaling pathways that play a crucial role in mediating rewarding behavioral effects of drugs. More interestingly, inflammatory responses in the central nervous system modulate the mesolimbic dopamine signaling and glutamate-dependent currents induced by addictive drugs. This review summarized researches in the alterations of inflammatory responses accompanied by rewarding and reinforcing properties of addictive drugs, including cocaine, methamphetamine, and opioids that were evaluated by conditioned place preference and self-administration procedures as highly common behavioral tests to investigate the motivational and reinforcing impacts of addictive drugs.

Graphical Abstract

The neuroinflammatory responses affect the rewarding properties of psychostimulants and opioids.

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Abbreviations

BBB:

Blood–brain barrier

BLA:

Basolateral amygdala

CNS:

Central nervous system

CPP:

Conditioned place preference

CCR:

CC chemokines

CCL2/MCP-1:

Chemokine monocyte chemotactic protein-1

CXCR:

CXC chemokines

CX3CR1:

CX3C-receptor 1

GABA:

γ-Aminobutyric acid

GDNF:

Glial cell-derived neurotrophic factor

IL:

Interleukin

KO:

Knockout

MyD88:

Myeloid differentiation factor 88

NSAID:

Nonsteroidal anti-inflammatory drug

NF-κB:

Nuclear factor-κβ

NAc:

Nucleus accumbens

PRRs:

Pattern recognition receptors

PDE:

Phosphodiesterase

PFC:

Prefrontal cortex

SA:

Self-administration

STAT3:

Signal transducer and activator of transcription 3

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor-alpha

VTA:

Ventral tegmental area

WT:

Wild-type

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Acknowledgements

The authors would like to thank the Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Funding

Financial support was solely provided by the authors.

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Contributions

AK-H and SC participated in the conception of the study, searched, screened, did the data extraction of the studies, drafted, and reviewed the manuscript. FN, AB-H, AH contributed to the conception of the study, reviewed, and edited the manuscript. AK-H and RM prepared tables. All authors read and confirmed the final version of the manuscript.

Corresponding author

Correspondence to Abbas Haghparast.

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Karimi-Haghighi, S., Chavoshinezhad, S., Mozafari, R. et al. Neuroinflammatory Response in Reward-Associated Psychostimulants and Opioids: A Review. Cell Mol Neurobiol 43, 649–682 (2023). https://doi.org/10.1007/s10571-022-01223-6

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  • DOI: https://doi.org/10.1007/s10571-022-01223-6

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