Carla Ghelardini (1), Nicoletta Galeotti (1), Alessandro Bartolini (1),
Shoei Furukawa (2), Atsumi Nitta (2), Dina Manetti (3) and Fulvio Gualtieri
(1) Department of Pharmacology, University of Florence, Viale G.B. Morgagni 65, I-50134 Florence, Italy
(2) Department of Molecular Biology, Gifu Pharmaceutical University, Mitahora-Higashi, Gifu 502-8585, Japan
(3) Department of Pharmaceutical Sciences, University of Florence, Via G. Capponi 9, I-50121 Florence, Italy
Abstract: The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (1O - 30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5 - 20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.
Keywords: PG-9, Learning, Memory, Nerve growth factor, Cholinergic system