Reversal of scopolamine-induced amnesia and alterations in energy metabolism by the nootropic piracetam: implications regarding identification of brain structures involved in consolidation of memory traces.
Pretreatment with scopolamine, 3 mg/kg, prevented the acquisition of a passive avoidance task in rats. These amnesic effects of scopolamine could largely be overcome by treatment with 100 mg/kg of the nootropic drug piracetam. In order to identify the brain structures involved, the effects of these drugs on regional energy metabolism were measured throughout the brain, utilizing Sokoloff's 2-deoxyglucose autoradiographic procedures. Scopolamine, 3 mg/kg, reduced glucose utilization in several areas of the cerebral cortex. These effects were largest in the parietal and temporal cortices. Other areas affected included the sensorimotor and cingulate cortices, the ventral and lateral thalamus, and the dendritic neuropil of the CA1, CA2, and CA3 regions of the hippocampus. The regional depressions in glucose metabolism observed following scopolamine treatment in the rat had some resemblance to depressions in glucose metabolism reported for Alzheimer's disease patients in positron emission tomography studies. Piracetam, 100 mg/kg, did not alter the energy metabolism of any of the 41 brain regions examined. However, this dose of piracetam completely reversed the scopolamine-induced depressions in the hippocampus. Piracetam partially but significantly reversed the scopolamine effects in the cingulate cortex. It is concluded that the data provide support for the hippocampal-cholinergic theory of memory as originally formulated by Meyers and Domino in 1964 and give insight into the mechanisms by which nootropics work.
Upjohn Company, Kalamazoo, MI 49001.
M F
MF
Piercey
G D
GD
Vogelsang
S R
SR
Franklin
A H
AH
Tang
D000647:Amnesia / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000378:metabolism; D004597:Electroshock; D004734:Energy Metabolism / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D009928:Organ Specificity; D010889:Piracetam / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D011760:Pyrrolidinones; D003847:Deoxyglucose; D012601:Scopolamine; D010889:Piracetam