Choline pivaloyl ester strengthened the benefit effects of Tacrine and Galantamine on electroencephalographic and cognitive performances in nucleus basalis magnocellularis-lesioned and aged rats

The aim of the present work was the assessment of the effects produced on the electroencephalographic (EEG) activity and the cognitive and memory performances of nucleus basalis magnocellularis (NBM)-lesioned or aged rats by the combined treatment with [2-(2,2-dimethylpropionyloxy)ethyl]trimethylammonium 2,2-dimethylpropionate (choline pivaloyl ester) (CPE) and the Cholinesterase inhibitors (ChEls) Tacrine (THA) and Galantamine (GAL). Intraperitoneal administration of CPE combined with THA or GAL to both NBM-lesioned or aged rats, produced EEG desynchronisation, and a significant decrease in the energy of the total EEG spectrum and the lower frequency bands (delta 0.25-3 and theta 4-7 Hz) lasting many minutes. Furthermore, drug associations reversed in aged rats the seopolaminne (0.2 mg/kg, i.p.)-induced increase in EEG power, slow waves and high-voltage spindle (HVS). Furthermore, the combined administration of CPE and Cholinesterase inhibitors in both NBM-lesioned or aged animals, improved performances in all behavioural tasks, enhancing object discrimination, increasing locomotory activity and alternation choice in T-maze, ameliorating retention in passive avoidance and decreasing escape latency in Morris water maze. In all test, AChEIs and CPE combinations proved to be more effective than CPE, THA or GAL given alone. In conclusion, the present work shows the ability of choline pivaloyl ester in strengthening the positive cerebral activity of THA and GAL. (c) 2006 Elsevier Inc. All rights reserved.