ObjectiveTo investigate the effects of chronic sleep deprivation (CSD) on the learning and memory abilities, brain dopamine(DA) content and D1 receptor expression in rat hippocampus and hypothalamus. MethodsHealthy adult male Sprague-Dawley (SD) rats were randomly divided into CSD group, treatment control(TC) group and blank control(BC) group after screening experiment. Each group included 10 rats. Rat CSD model was established by modified multiple platform method (MMPM), in which the rats were subjected to 18 h/d sleep deprivation(PM16:00-AM10:00)for 21 days. Rats in TC group were given similar deprivation as CSD group, but lived in a deprivation box with bottom covered with wire grid. The learning and memory abilities of rats were measured by Morris water maze and open-field test at CSD 7, 14, and 21 d. DA content and D1 receptor protein expression in hippocampus and hypothalamus were determined by high performance liquid chromatography-electrochemical detector (HPLC-ECD) and Western blotting analysis, respectively. ResultsCompared with BC and TC groups, CSD rats were exhausted and irritated, without sleek hair. The weight of CSD rats were decreased significantly from the third day of sleep deprivation (P<0.01). The escape latency in Morris water maze of CSD group was increased significantly and the platform crossings decreased significantly compared with those of the other two groups (P<0.01). The spontaneous motor activity distance and activity times were also significantly decreased in CSD group(P<0.05). The hippocampus and hypothalamus DA content and D1 receptor protein expression were significantly decreased in CSD group as determined by HPLC-ECD and Western blotting analysis (P<0.05). As expected, there were no significant differences in the above parameters between BC and TC group. ConclusionCSD can impair the learning and memory abilities in rats. Decreased dopamine and D1 receptor in hippocampus and hypothalamus may be involved in modulating the learning and memory dysfunction.