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Recent clinical studies indicate neurobehavioral disturbances in type-2 diabetics. However, there is paucity of preclinical research to support this concept. The validity of db/db mouse as an animal model to study type-2 diabetes and related complications is known. The present study was designed to investigate comprehensively the db/db mouse behavior as preclinical evidence of type-2 diabetes related major neurobehavioral complications. We tested juvenile (5–6 weeks) and adult (10–11 weeks) db/db mice for behavioral depression in forced swim test (FST), psychosis-like symptoms using pre-pulse inhibition (PPI) test, anxiety behavior employing elevated plus maze (EPM) test, locomotor behavior and thigmotaxis using open field test and working memory deficits in Y-maze test. Both juvenile and adult group db/db mice displayed behavioral despair with increased immobility time in FST. There was an age-dependent progression of psychosis-like symptoms with disrupted PPI in adult db/db mice. In the EPM test, db/db mice were less anxious as observed by increased percent open arms time and entries. They were also hypolocomotive as evident by a decrease in their basic and fine movements. There was no impairment of working memory in the Y-maze test in db/db mice. This is the first report of depression, psychosis-like symptoms and anxiolytic behavior of db/db mouse strain. It is tempting to speculate that this mouse strain can serve as useful preclinical model to study type-2 diabetes related neurobehavioral complications.

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Abstract-The objective of this study was to determine the effect of chronic stress exposure on the circadian pattern of cardiovascular responses in mice. Using male C57BL6 mice with carotid arterial catheters, we tested the effect of 7 days of intermittent shaker stress on body weight, food intake, drinking activity, plasma corticosterone, mean arterial pressure (MAP), and heart rate. The stress was delivered automatically for 2-minute periods (150 cycles/min), 45 times/d for 7 days. Plasma corticosterone was significantly increased in acutely and chronically stressed mice, with a partial attenuation in the chronic condition. Stress increased water intake, produced no change in food intake, and significantly decreased body weight (5% change). MAP and heart rate were measured continuously on stress days 1, 3, and 7 and during the basal and recovery periods. Chronic stress did not produce a sustained increase in MAP; however, there was an increase in MAP during the first stress day and a decrease during the recovery period. There was a circadian pattern in the pressor responses, with greater increases seen during the light period (nonactive phase) than in the dark period (ϩ24% versus ϩ11% on stress day 3, light versus dark). The results suggest that a stress delivered during the nonactive phase represents a higher cardiovascular risk. Key Words: blood pressure Ⅲ heart rate Ⅲ corticosterone Ⅲ circadian rhythm L ifestyle stress is a risk factor for human diseases, including cancer, stroke, psychological disorders, and heart disease. There is a circadian pattern in the incidence of cardiovascular pathologies, with a higher frequency of heart attacks, strokes, and arrhythmias during the morning hours. [1][2][3] Stressful conditions may also be a precipitating factor in the occurrence of cardiovascular accidents.In animals, stress exposure produced by a variety of methods provokes a cascade of autonomic adjustments characterized by increased blood pressure (BP), increased heart rate (HR), and behavioral alterations. Most studies of stress biology have been conducted in rats, providing information on changes in cardiovascular function and eating and drinking behaviors. 4 -10 However, one complication of the experimental paradigms is that the stress effects can be enhanced by animal handling, noise, or pain, as seen in the forced swim test, air jet exposure, and physical restraint. 4,8,11 Shaker stress is a mild, pain-free stimulus that elicits reproducible changes in BP, HR, sympathetic activity, and stress hormone secretion. 12,13 There is no information on the application of shaker stress in mice and no data on the long-term effects of shaker stress on the cardiovascular system or on drinking and eating patterns.For investigations in mice, we developed a computerized system for chronic, continuous BP recording and combined this with electronic recording of licking activity for analysis of circadian patterns. 14,15 This methodology was applied to the investigation of the effects of stress on BP and HR responses and dri...

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