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Cocaine-related behaviors in mice with deficient gliotransmission

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Abstract

Rationale

Astrocytes play an integral role in modulating synaptic transmission and plasticity, both key mechanisms underlying addiction. However, while astrocytes are capable of releasing chemical transmitters that can modulate neuronal function, the role of these gliotransmitters in mediating behaviors associated with drugs of abuse has been largely unexplored.

Objectives

The objective of the present study was to utilize mice with astrocytes that lack the ability to release chemical transmitters to evaluate the behavioral consequence of impaired gliotransmission on cocaine-related behaviors. These mice have previously been used to examine the role of gliotransmission in sleep homeostasis; however, no studies to date have utilized them in the study of addictive behaviors.

Methods

Mice expressing a dominant-negative SNARE protein selectively in astrocytes (dnSNARE mice) were tested in a variety of behavioral paradigms examining cocaine-induced behavioral plasticity. These paradigms include locomotor sensitization, conditioned place preference followed by cocaine-induced reinstatement of CPP, and cocaine self-administration followed by cue-induced reinstatement of cocaine-seeking behavior.

Results

Wild-type and dnSNARE mice demonstrated no significant differences in the development or maintenance of locomotor sensitization. While there were non-significant trends for reduced CPP following a low dose of cocaine, drug-induced reinstatement of CPP is completely blocked in dnSNARE mice. Similarly, while dnSNARE mice demonstrated a non-significant trend toward reduced cocaine self-administration compared with wild-type mice, dnSNARE mice do not demonstrate cue-induced reinstatement in this paradigm.

Conclusions

Gliotransmission is necessary for reinstatement of drug-seeking behaviors by cocaine or associated cues.

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Acknowledgments

This work was supported by the National Institutes of Health National Institute on Drug Abuse [grants R01-DA025967 (PH, JAB), F32-DA026236 (JRT), F32-DA026660 (LAB), and T32-DA028874 (LE)]. We thank Dr. Chris Pierce for generously providing use of the mouse self-administration chambers. We thank Dr. Monica Hilario and Dr. Heath Schmidt for their helpful discussion of the data presented.

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Authors and Affiliations

  1. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Jill R. Turner, Laurel E. Ecke, Lisa A. Briand & Julie A. Blendy

  2. Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Laurel E. Ecke

  3. Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA

    Philip G. Haydon

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  1. Jill R. Turner
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  2. Laurel E. Ecke
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  3. Lisa A. Briand
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  4. Philip G. Haydon
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  5. Julie A. Blendy
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Correspondence to Julie A. Blendy.

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Turner, J.R., Ecke, L.E., Briand, L.A. et al. Cocaine-related behaviors in mice with deficient gliotransmission. Psychopharmacology 226, 167–176 (2013). https://doi.org/10.1007/s00213-012-2897-4

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  • DOI: https://doi.org/10.1007/s00213-012-2897-4

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