title: Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.
abstract: Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences (CCS), Federal University of Santa Maria, Santa Maria, RS, CEP 97105-900, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Marisco
authors.forename: Fabiano B
authors.initials: FB
authors.lastname: Carvalho
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rosa
authors.forename: Bruna A
authors.initials: BA
authors.lastname: Girardi
authors.forename: Jessié M
authors.initials: JM
authors.lastname: Gutierres
authors.forename: Jeandre A S
authors.initials: JA
authors.lastname: Jaques
authors.forename: Ana P S
authors.initials: AP
authors.lastname: Salla
authors.forename: Víctor C
authors.initials: VC
authors.lastname: Pimentel
authors.forename: Maria Rosa C
authors.initials: MR
authors.lastname: Schetinger
authors.forename: Daniela B R
authors.initials: DB
authors.lastname: Leal
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Mello
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010889:Piracetam / Q000494:pharmacology*; D011755:Pyrophosphatases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology*; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D000255:Adenosine Triphosphate; D012601:Scopolamine; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D011755:Pyrophosphatases; D000241:Adenosine; D010889:Piracetam