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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.
Biol Psychiatry 2016; 80(3):207-15BP

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.

Authors+Show Affiliations

Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: reissner@unc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26946381

Citation

Scofield, Michael D., et al. "Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core." Biological Psychiatry, vol. 80, no. 3, 2016, pp. 207-15.
Scofield MD, Li H, Siemsen BM, et al. Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core. Biol Psychiatry. 2016;80(3):207-15.
Scofield, M. D., Li, H., Siemsen, B. M., Healey, K. L., Tran, P. K., Woronoff, N., ... Reissner, K. J. (2016). Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core. Biological Psychiatry, 80(3), pp. 207-15. doi:10.1016/j.biopsych.2015.12.022.
Scofield MD, et al. Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core. Biol Psychiatry. 2016 08 1;80(3):207-15. PubMed PMID: 26946381.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cocaine Self-Administration and Extinction Leads to Reduced Glial Fibrillary Acidic Protein Expression and Morphometric Features of Astrocytes in the Nucleus Accumbens Core. AU - Scofield,Michael D, AU - Li,Hao, AU - Siemsen,Benjamin M, AU - Healey,Kati L, AU - Tran,Phuong K, AU - Woronoff,Nicholas, AU - Boger,Heather A, AU - Kalivas,Peter W, AU - Reissner,Kathryn J, Y1 - 2015/12/31/ PY - 2015/08/17/received PY - 2015/12/02/revised PY - 2015/12/17/accepted PY - 2016/3/7/entrez PY - 2016/3/8/pubmed PY - 2017/8/8/medline KW - Astrocyte KW - Cocaine KW - Colocalization KW - GFAP KW - Nucleus accumbens KW - Self-administration SP - 207 EP - 15 JF - Biological psychiatry JO - Biol. Psychiatry VL - 80 IS - 3 N2 - 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. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/26946381/Cocaine_Self-Administration_and_Extinction_Leads_to_Reduced_Glial_Fibrillary_Acidic_Protein_Expression_and_Morphometric_Features_of_Astrocytes_in_the_Nucleus_Accumbens_Core L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(15)01087-2 DB - PRIME DP - Unbound Medicine ER -