| Autor: |
Roodsari SK; Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Cheng Y; Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Reed KM; Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Wellman LL; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Sanford LD; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Kim WK; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA., Guo ML; Drug Addiction Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.; Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA. |
| Abstrakt: |
Sleep disorders have high comorbidity with drug addiction and function as major risk factors for developing drug addiction. Recent studies have indicated that both sleep disturbance (SD) and abused drugs could activate microglia, and that increased neuroinflammation plays a critical role in the pathogenesis of both diseases. Whether microglia are involved in the contribution of chronic SDs to drug addiction has never been explored. In this study, we employed a mouse model of sleep fragmentation (SF) with cocaine treatment and examined their locomotor activities, as well as neuroinflammation levels and dopamine signaling in the striatum, to assess their interaction. We also included mice with, or without, SF that underwent cocaine withdrawal and challenge. Our results showed that SF significantly blunted cocaine-induced locomotor stimulation while having marginal effects on locomotor activity of mice with saline injections. Meanwhile, SF modulated the effects of cocaine on neuroimmune signaling in the striatum and in ex vivo isolated microglia. We did not observe differences in dopamine signaling in the striatum among treatment groups. In mice exposed to cocaine and later withdrawal, SF reduced locomotor sensitivity and also modulated neuroimmune and dopamine signaling in the striatum. Taken together, our results suggested that SF was capable of blunting cocaine-induced psychoactive effects through modulating neuroimmune and dopamine signaling. We hypothesize that SF could affect neuroimmune and dopamine signaling in the brain reward circuitry, which might mediate the linkage between sleep disorders and drug addiction. |
