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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Article info
Publication history
Published online: December 31, 2015
Accepted:
December 17,
2015
Received in revised form:
December 2,
2015
Received:
August 17,
2015
Footnotes
☆HL and BS contributed equally to this work.
Identification
Copyright
© 2016 Society of Biological Psychiatry.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Astrocytes: The Stars of Extinction-Related Learning or Cocaine-Induced Brain Plasticity?Biological PsychiatryVol. 80Issue 3
- PreviewAlthough 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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