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The Differential Effects of Chronic Alcohol and Cigarette Smoke Exposures on Cognitive-Behavioral Dysfunction in Long Evans Rats

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Journal of Behavioral and Brain Science 2022年第9期12卷 413-432页

作者： Emine B. Yalcin Büşra Nur Delikkaya william.pelit Ming Tong Suzanne M. De La Monte Sharon Rounds Division of Research Providence VA Medical Center Providence RI USA Liver Research Center Division of Gastroenterology and Department of Medicine Rhode Island Hospital and the Alpert Medical School of Brown University Providence RI USA Chemical Biology and English Brown University Providence RI USA Departments of Medicine Neurology and Pathology and Laboratory Medicine Rhode Island Hospital Women & Infants Hospital of Rhode Island Alpert Medical School of Brown University Providence VA Medical Center Providence RI USA Departments of Medicine and Pathology and Laboratory Medicine Warren Alpert Medical School of Brown University Vascular Research Laboratory Providence VA Medical Center Providence RI USA

Background and Objective: Chronic heavy alcohol consumption and daily cigarette smoking are the most prevalent substance use problems in the U.S., including Veterans. Excessive alcohol use causes neurocognitive and behavioral deficits that can be linked to neurodegeneration. Similarly, preclinical and clinical data suggest that smoking also leads to brain atrophy. This study examines the differential and additive effects of alcohol and cigarette smoke (CS) exposures on cognitive-behavioral function. Methods: A 4-way experimental model of chronic alcohol and CS exposures was generated using 4-week-old male and female Long Evans rats that were pair-fed with Lieber-deCarli isocaloric liquid diets containing 0% or 24% ethanol for 9 weeks. Half of the rats in the control and ethanol groups were exposed to CS for 4 hours/day and 4 days/week for 9 weeks. All rats were subjected to Morris Water Maze, Open Field, and Novel Object Recognition testing in the last experimental week. Results: Chronic alcohol exposure impaired spatial learning as shown by significantly increased latency to locate the platform, and it caused anxiety-like behavior marked by the significantly reduced percentage of entries to the center of the arena. Chronic CS exposure impaired recognition memory as suggested by significantly less time spent at the novel object. Combined exposures to alcohol and CS did not show any significant additive or interactive effect on cognitive-behavioral function. Conclusion: Chronic alcohol exposure was the main driver of spatial learning, while the effect of secondhand CS exposure was not robust. Future studies need to mimic direct CS exposure effects in humans.

关键词： Alcohol Cigarette Smoke Spatial Learning Recognition Memory Anxiety White Matter Rat

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