title: Rosiglitazone treatment reversed depression- but not psychosis-like behavior of db/db diabetic mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, USA.
authors.forename: Ajaykumar N
authors.initials: AN
authors.lastname: Sharma
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Elased
authors.forename: James B
authors.initials: JB
authors.lastname: Lucot
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004644:Emotions / Q000187:drug effects; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009043:Motor Activity / Q000187:drug effects; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism; D000077154:Rosiglitazone; D013550:Swimming; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D001786:Blood Glucose; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone