Cocaine Administration and Its Abstinence Conditions Modulate Neuroglia.

Kinga Gawlińska,Małgorzata Frankowska,Małgorzata Filip,Marcin Piechota,Dawid Gawliński,Michał Korostyński

doi:10.3390/ijms21217970

Kinga Gawlińska, Małgorzata Frankowska + Show 4 more

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https://doi.org/10.3390/ijms21217970

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Abstract

Cocaine induces neuronal changes as well as non-neuronal (astrocytes, microglia, oligodendroglia) mechanisms, but these changes can also be modulated by various types of drug abstinence. Due to the very complex and still incompletely understood nature of cocaine use disorder, understanding of the mechanisms involved in addictive behavior is necessary to further search for effective pharmacotherapy of this disease. The aim of this study was to investigate changes at the gene and protein levels associated with glial cell activity after cocaine exposure, as well as during early cocaine abstinence (3 days) with extinction training or in home cage isolation. Cocaine self-administration significantly decreased myelin regulatory factor (MYRF) and cyclic nucleotide phosphodiesterase (CNP) expression in the hippocampus as well as pleckstrin (PLEK) and T-lymphocyte activation antigen (CD86) in the rat striatum. Depending on cocaine abstinence conditions, microglial PLEK expression was increased through extinction training but did not change in the home cage isolation. In addition, downregulation of gene expression associated with oligodendrocytes (CNP, MYRF) and microglia regulator of G protein signaling 1 (RGS1) was observed in the hippocampus, regardless of the type of drug abstinence, while downregulation of myelin and lymphocyte protein (MAL) expression was found only in rats exposed to abstinence in the home cage. Taken together, the presented results strongly suggest that cocaine abstinence evokes significant changes in gene expression associated with the proper functioning of glial cells, suggesting their significant involvement in adaptive changes in the brain associated with cocaine exposure. Interestingly, drug abstinence conditions are important factors influencing observed changes at the transcript levels of selected genes, which may be of clinical interest.

Highlights

Substance use disorder (SUD), which is a serious threat to public health, is a multifaceted disorder
The most significant changes in transcript levels were observed on the third day of cocaine abstinence within the striatum and the hippocampus, and we focused on the effects of the early abstinence period
There were significant changes in selected transcript levels associated with oligodendroglia, such as: myelin and lymphocyte (Mal) (F(2, 9) = 8.84, p < 0.01), myelin transcription factor (Myrf) (F(2, 9) = 18.45, p < 0.001), and cyclic nucleotide phosphodiesterase (Cnp) (F(2, 9) = 8.51, p < 0.01) within the hippocampus, but not changes within the prefrontal cortex and striatum

Summary

Introduction

Substance use disorder (SUD), which is a serious threat to public health, is a multifaceted disorder. Microglial cells, not directly participating in the modulation of neurotransmission, express numerous molecules associated with inflammation that become activated by neuronal injury or degeneration and express multiple receptors for neuropeptides and neurotransmitters capable of releasing trophic factors that are important in the survival of neurons [10,11]. The latter cells are activated following chronic cocaine treatment, leading to inflammatory responses in animal models [12] and in clinical studies [13]

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