Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell

Bernadette O'Donovan, Austin Neugornet, Richik Neogi, Mengfan Xia, Pavel Ortinski

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Astrocytes have become established as an important regulator of neuronal activity in the brain. Accumulating literature demonstrates that cocaine self-administration in rodent models induces structural changes within astrocytes that may influence their interaction with the surrounding neurons. Here, we provide evidence that cocaine impacts astrocytes at the functional level and alters neuronal sensitivity to astrocyte-derived glutamate. We report that a 14-day period of short access to cocaine (2 h/day) decreases spontaneous astrocytic Ca2+ transients and precipitates changes in astrocyte network activity in the nucleus accumbens shell. This is accompanied by increased prevalence of slow inward currents, a physiological marker of neuronal activation by astrocytic glutamate, in a subset of medium spiny neurons. Within, but not outside, of this subset, we observe an increase in duration and frequency of N-methyl-D-aspartate (NMDA) receptor-mediated synaptic events. Additionally, we find that the link between synaptic NMDA receptor plasticity and neuron sensitivity to astrocytic glutamate is maintained independent of drug exposure and is observed in both cocaine and saline control animals. Imaging analyses of neuronal Ca2+ activity show no effect of cocaine self-administration on individual cells or on neuronal network activity in brain slices. Therefore, our data indicate that cocaine self-administration promotes astrocyte-specific functional changes that can be linked to increased glutamate-mediated coupling with principal neurons in the nucleus accumbens. Such coupling may be spatially restricted as it does not result in a broad impact on network structure of local neuronal circuits.

Original languageEnglish
Article numbere13042
JournalAddiction Biology
Issue number6
StatePublished - Nov 2021

Bibliographical note

Funding Information:
National Institute on Drug Abuse, Grant/Award Number: DA041513

Publisher Copyright:
© 2021 Society for the Study of Addiction


  • astrocyte
  • cocaine self-administration
  • synaptic plasticity

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health


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