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Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core

Published:December 31, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.12.022

      Abstract

      Background

      As a more detailed picture of nervous system function emerges, diversity of astrocyte function becomes more widely appreciated. While it has been shown that cocaine experience impairs astroglial glutamate uptake and release in the nucleus accumbens (NAc), few studies have explored effects of self-administration on the structure and physiology of astrocytes. We investigated the effects of extinction from daily cocaine self-administration on astrocyte characteristics including glial fibrillary acidic protein (GFAP) expression, surface area, volume, and colocalization with a synaptic marker.

      Methods

      Cocaine or saline self-administration and extinction were paired with GFAP Westerns, immunohistochemistry, and fluorescent imaging of NAc core astrocytes (30 saline-administering and 36 cocaine-administering male Sprague Dawley rats were employed). Imaging was performed using a membrane-tagged lymphocyte protein tyrosine kinase-green fluorescent protein (Lck-GFP) driven by the GFAP promoter, coupled with synapsin I immunohistochemistry.

      Results

      GFAP expression was significantly reduced in the NAc core following cocaine self-administration and extinction. Similarly, we observed an overall smaller surface area and volume of astrocytes, as well as reduced colocalization with synapsin I, in cocaine-administering animals. Cocaine-mediated reductions in synaptic contact were reversed by the β-lactam antibiotic ceftriaxone.

      Conclusions

      Multiple lines of investigation indicate that NAc core astrocytes exist in a hyporeactive state following cocaine self-administration and extinction. Decreased association with synaptic elements may be particularly meaningful, as cessation of chronic cocaine use is associated with changes in synaptic strength and resistance to the induction of synaptic plasticity. We hypothesize that the reduced synaptic colocalization of astrocytes represents an important maladaptive cellular response to cocaine and the mechanisms underlying relapse vulnerability.

      Keywords

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      Linked Article

      • Astrocytes: The Stars of Extinction-Related Learning or Cocaine-Induced Brain Plasticity?
        Biological PsychiatryVol. 80Issue 3
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          Although they were originally considered mere support cells for neurons (1), it is now apparent that glia, particularly astrocytes, are capable of synthesizing and releasing both amino acid and purinergic transmitters and can bidirectly communicate with neurons (2). So named for their star shape, astrocytic regulation of excitatory synaptic transmission and neuroplasticity by the modulation of synaptic and extrasynaptic glutamate is particularly well documented (2). As such, research concerning how genetic and environmental factors interact to influence astrocyte function in vivo is vital to our understanding of the basic cellular biology of the nervous system, as well as the contribution of anomalous gliotransmission to nervous system disorders.
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