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2026

bioRxiv 2026 Jan 13. doi: 10.64898/2026.01.12.699167

Disrupting astrocyte signalling in the nucleus accumbens impairs incentive-driven instrumental actions

Joanne M. Gladding, Octavia Soegyono, Arvie Rodriguez, Abiero, Karly M. Turner, Michael D. Kendig, Laura A. Bradfield

School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, New South Wales 2007, Australia. Department of Psychology, University of Sydney, Sydney, New South Wales 2006, Australia. School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.

Service type: Stock strains

Abstract

Astrocytes in the nucleus accumbens (NAC) core have been observed to undergo phenotypic changes associated with drug-seeking behaviour in both humans and animals. However, the role of NAC core astrocytes in non-drug-related instrumental behaviour remains poorly understood. To address this, we chemogenetically activated hM4Di receptors selectively expressed on NAC core astrocytes in rats during food-motivated decision-making tasks. In Experiment 1, rats were first trained to associate two auditory stimuli with two distinct food outcomes (pellets and sucrose), then to press left and right levers for those same outcomes. All training was conducted drug-free, and rats then received intraperitoneal (i.p) injections of either vehicle or deschloroclozapine (DCZ) prior to test. Disrupting astrocytic signalling via DCZ injections left instrumental choice intact when it was guided by cues signalling the sensory-specific properties of each outcome, as tested in specific Pavlovian instrumental transfer and outcome-selective reinstatement, but suppressed responding in an outcome devaluation test. In Experiment 2, a single stimulus and single lever were separately paired with distinct food outcomes, then presented together on test. Control animals demonstrated a general PIT effect, elevating responding during stimulus presentations, and this was prevented by Gi activation on NAC core astrocytes. Immunohistochemistry revealed increased neuronal activity following hM4Di activation in astrocytes. Together, these findings suggest that intact signalling in NAC core astrocytes is necessary for instrumental actions that depend on general arousal or affective processes, but not for actions guided by sensory-specific outcome expectations.