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Dehydration is a powerful stimulus causing disequilibrium in homeostasis of water and electrolytes resulting from depletion in total body water. Most studies have focused on domestic and laboratory animals; however, the study of desert animals allows improved understanding about water balance and resistance to dehydration and associated behavioral changes, including those related to mood disorders. Meriones shawi (Shaw’s Jird) is a desert rodent characterized by its resistance to long periods of thirst that can extend for several months. In the present study, M. shawi were subjected to water deprivation for 1 and 3 months. We used 5-HT immunohistochemistry to evaluate the effects of prolonged dehydration on the serotoninergic system in both dorsal and median raphe nuclei (DRN, MRN), which are the main sources of 5-HT input to several brain areas. In addition, a dark/light box was used to evaluate the anxiolytic-like or anxiogenic-like effects of dehydration on M. shawi. The results showed a reduction in the 5-HT immunolabelling in both DRN and MRN following 1 and 3 months of dehydration. This diminution of serotonin immunoreactivity was accompanied by noticeable changes in anxiety behavior of Meriones, with animals spending more time in the light box, suggesting anxiogenic-like effects caused by dehydration. Overall, the results indicate that dehydration is able to reduce serotoninergic neurotransmission, which might be involved in generating anxiety behavior in this desert animal. (C) 2011 Published by Elsevier GmbH.