title: Behavioral deficits in rats following acute administration of glimepiride: Relationship with brain serotonin and dopamine.
abstract: A considerable body of literature suggests that depression and diabetes mellitus are co-morbid. The present study was designed to test any possible behavioral deficits and/or neurochemical changes in the brain as induced by the anti-diabetic drugs. Twenty-four rats were divided into four groups: (i) saline (ii) glimepiride (2.5mg/kg)- (iii) glimepiride (5.0mg/kg)- and (iv) glimepiride (10 mg/kg) injected animals. Behavioral activities in Skinner's box, open field and elevated plus maze were monitored 20, 35 and 45 minutes post injection respectively. Animals were decapitated 60 minutes post injection to collect brain samples. Samples were kept at -70°C until neurochemical analysis by HPLC-EC. Results from the present study show decreased time spent in the open arm of the elevated plus maze (p<0.05) at all the three doses. A decrease in the HVA (Homovanillic acid) levels at all three doses (p<0.01) was also observed along with decreased 5-HT (5-Hydroxytryptamine) (p<0.05 at 5.0 and 10mg/kg) and 5-HIAA (5-Hydroxyindoleacetic acid) (p<0.05 at all three doses) levels. Since a decrease in 5-HT metabolism can induce depression-like effects, the present study therefore suggests that the occurrence of depression in diabetic patients is due to the use of glimipride. Effects of long-term administration of smaller doses of glimipride are to be explored further to monitor tolerance in glimipride-induced deficits of serotonin. The finding may help to explore the cause of depression in diabetics for improving pharmacotherapy in diabetes.
authors.affiliation: Department of Biochemistry, Liaquat National Medical College, Karachi, Pakistan / Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Shehnaz Abdul
authors.initials: SA
authors.lastname: Sheikh
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Huma
authors.initials: H
authors.lastname: Ikram
authors.affiliation: Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan / Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi, Pakistan.
authors.forename: Darakhshan Jabeen
authors.initials: DJ
authors.lastname: Haleem
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D012701:Serotonin; C057619:glimepiride; D004298:Dopamine