Work

Incentive-driven instrumental actions depend on intact astrocytic signalling in nucleus accumbens core

Year: 2026

Type: article

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 male and female 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 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. Significance Statement Astrocyte dysfunction in the nucleus accumbens (NAC) has been implicated in several forms of compulsion in humans, yet preclinical work has focussed almost exclusively on drug-taking and seeking. The role of NAC core astrocytes on responding for non-drug outcomes is therefore unclear. Here, using food outcomes, we show that agonising Gi receptors on astrocytes in NAC core selectively impairs actions driven by general motivational states but spares those guided by specific outcome expectations. These findings suggest that NAC core astrocytes play a critical role in invigorating behaviour, extending their involvement beyond drug-seeking in animals and highlighting their potential relevance to compulsive behaviour more generally.

Source: eNeuro

DOI: 10.1523/eneuro.0341-26.2026