title: Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.
abstract: Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.
authors: Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, 281 406, India.
authors: Shruti
authors: S
authors: Pandey
authors: Division of Pharmacology, Institute of Pharmaceutical Research, GLA University, Mathura, 281 406, India. debapriya.garabadu@gla.ac.in.
authors: Debapriya
authors: http://orcid.org/0000-0002-4235-3926
authors: D
authors: Garabadu
mesh_terms: D000647:Amnesia / Q000150:complications / Q000188:drug therapy*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001927:Brain Diseases / Q000150:complications / Q000188:drug therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008568:Memory / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D010889:Piracetam / Q000494:pharmacology / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D007328:Insulin; D008687:Metformin; D000071679:Glycogen Synthase Kinase 3 beta; D002794:Choline; D010889:Piracetam
keywords: Hippocampus; Memory; Metformin; Piracetam; Pre-frontal cortex; Type-2 diabetes mellitus