In vivo calcium extrusion from accumbal astrocytes reduces anxiety-like behaviors but increases compulsive-like responses and compulsive ethanol drinking in mice

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2025-01-20 DOI:10.1016/j.neuropharm.2025.110320

Lee Peyton , Humza Haroon , Anthony Umpierre , Hesham Essa , Robert Bruce , Long-Jun Wu , Doo-Sup Choi

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Abstract

The ventral striatum is crucially involved in reward processing. The present study investigates the behavioral effects of astrocyte-specific calcium extrusion virus “CalEx” on perseverative responses in the operant five-choice serial reaction time task and ethanol-conditioned place preference. Mice were injected with CalEx via the GfaABC₁D promoter to extrude cytosolic calcium from astrocytes within the ventral striatum. We found that CalEx transfection in the ventral striatum reduced evoked response duration, the maximum amplitude, and the response frequency to 500 μM ATP as measured by ΔF/F fluorescence intensity of the genetically encoded calcium indicator targeting astrocytes GCaMP6f. During the five-choice serial reaction time task, CalEx mice persisted in perseverative responses compared to their counterparts. Additionally, during ethanol-conditioned place preference, CalEx mice showed increased place preference for a low ethanol concentration compared to control group. Furthermore, we found that accumbal astrocytic calcium extrusion increased quinine adulterated ethanol drinking. Our findings suggest that diminishing ventral striatum astrocyte calcium activity contributes to compulsive behaviors, ethanol drinking, and enhanced ethanol drug reward.

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).