Rosiglitazone treatment reversed depression- but not psychosis-like behavior of db/db diabetic mice

• Published in: Journal of psychopharmacology (Oxford) Vol. 26; no. 5; p. 724
• Main Authors: Sharma, Ajaykumar N, Elased, Khalid M, Lucot, James B
• Format: Journal Article
• Language: English
• Published: United States 01.05.2012
• Subjects: Animals; Antidepressive Agents - pharmacology; Blood Glucose - metabolism; Depressive Disorder - drug therapy; Depressive Disorder - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - psychology; Emotions - drug effects; Glucose Tolerance Test; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; Hyperglycemia - psychology; Insulin - metabolism; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Motor Activity - drug effects; Psychotic Disorders - drug therapy; Psychotic Disorders - metabolism; Swimming; Thiazolidinediones - pharmacology
• ISSN: 1461-7285
• DOI: 10.1177/0269881111434620

The objective of the present study was to examine the effect of long-term management of insulin resistance and hyperglycemia on neurobehavioral deficits in db/db mice. In this study, 5-week-old db/db and lean control mice were fed with rosiglitazone (20 mg/kg/day) mixed or standard chow for a duration of 5 weeks. Mice were monitored weekly for blood glucose concentration. Five weeks after the onset of treatment, they were subjected to the forced swim test (FST), pre-pulse inhibition (PPI), open field test (OFT) and fear-potentiated startle (FPS) test to examine for depression, psychosis-like behavior, locomotor activity and emotional learning, respectively. Rosiglitazone normalized hyperglycemia and improved glucose tolerance. Rosiglitazone significantly reduced immobility time in the FST in db/db mice, suggesting an antidepressant-like effect. However, rosiglitazone failed to reverse disruption of PPI in db/db mice, indicating its ineffectiveness against psychosis-like behavior. In the OFT, rosiglitazone did not affect the activity of db/db mice, suggesting its antidepressant-like effect was independent of changes in locomotor activity. In the FPS test, db/db mice showed impaired emotional learning and rosiglitazone failed to correct it. In conclusion, long-term blood glucose management in type-2 diabetics may help to limit the co-occurrence of depression but not the psychotic symptoms and ability to cope with stress.