Reducing astrocyte calcium in the nucleus accumbens core increases reward valuation

Abstract

Astrocyte dysfunction within the nucleus accumbens (NAc) has been increasingly implicated in maladaptive reward processing and the development of addiction-like behaviors. In this study, we investigated how impairing astrocyte calcium signaling in the NAc core influences consummatory reward behaviors and reward valuation. Using a viral approach to express the human plasma membrane calcium ATPase (hPMCA) in NAc core astrocytes in male rats, we selectively reduced intracellular astrocyte calcium dynamics. Blunting astrocyte calcium signaling led to increased self-administration of both sucrose and cocaine on a low effort fixed-ratio schedule of reinforcement. Behavioral economic analysis revealed enhanced reward motivation and valuation in hPMCA-expressing rats as compared to controls. Notably, reduction of astrocyte calcium signaling did not alter cocaine-induced locomotor sensitization, indicating a dissociation between astrocytic regulation of reward valuation and other cocaine-related behaviors. Collectively, these results identify astrocyte calcium dynamics in the NAc core as a key constraint on motivational drive and reward valuation.