Abstract
Recent literature supports a prominent role for astrocytes in regulation of drug-seeking behaviors. The dorsal striatum, specifically, is known to play a role in reward processing with neuronal activity that can be influenced by astrocyte Ca2+. However, the manner in which Ca2+ in dorsal striatum astrocytes impacts neuronal signaling after exposure to self-administered cocaine remains unclear. We addressed this question following over-expression of the Ca2+ extrusion pump, hPMCA2w/b, in dorsal striatum astrocytes and the Ca2+ indicator, GCaMP6f, in dorsal striatum neurons of rats that were trained to self-administer cocaine. Following extinction of cocaine-seeking behavior, the rats over-expressing hMPCA2w/b showed a significant increase in cue-induced reinstatement of cocaine seeking. Suppression of astrocyte Ca2+ increased the amplitude of neuronal Ca2+ transients in brain slices, but only after cocaine self-administration. This was accompanied by decreased duration of neuronal Ca2+ events in the cocaine group and no changes in Ca2+ event frequency. Acute administration of cocaine to brain slices decreased amplitude of neuronal Ca2+ in both the control and cocaine self-administration groups regardless of hPMCA2w/b expression. These results indicated that astrocyte Ca2+ control over neuronal Ca2+ transients was enhanced by cocaine self-administration experience, although sensitivity to acutely applied cocaine remained comparable across all groups. To explore this further, we found that neither the hMPCA2w/b expression nor the cocaine self-administration experience altered regulation of neuronal Ca2+ events by NPS-2143, a Ca2+ sensing receptor (CaSR) antagonist, suggesting that plasticity of neuronal signaling after hPMCA2w/b over-expression was unlikely to result from elevated extracellular Ca2+. We conclude that astrocyte Ca2+ in the dorsal striatum impacts neurons via cell-intrinsic mechanisms (e.g., gliotransmission, metabolic coupling, etc.) and impacts long-term neuronal plasticity after cocaine self-administration differently from neuronal response to acute cocaine. Overall, astrocyte Ca2+ influences neuronal output in the dorsal striatum to promote resistance to cue-induced reinstatement of cocaine seeking.
Document Type
Article
Publication Date
2024
Digital Object Identifier (DOI)
https://doi.org/10.3389/fncel.2024.1347491
Funding Information
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by DA053070 (PO, MB), DA035200 (TA), and DA055445 (TA).
Repository Citation
Tavakoli, Navid S.; Malone, Samantha G.; Anderson, Tanner L.; Neeley, Ryson E.; Asadipooya, Artin; Bardo, Michael T.; and Ortinski, Pavel I., "Astrocyte Ca2+ in the dorsal striatum suppresses neuronal activity to oppose cue-induced reinstatement of cocaine seeking" (2024). Psychology Faculty Publications. 223.
https://uknowledge.uky.edu/psychology_facpub/223
Notes/Citation Information
© 2024 Tavakoli, Malone, Anderson, Neeley, Asadipooya, Bardo and Ortinski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.