Prolonged treatment with alpha-glycerylphosphorylethanolamine facilitates the acquisition of an active avoidance behavior and selectively increases neuronal signal transduction in rats.
The effects of alpha-glycerylphosphorylethanolamine on both behavioral and neurochemical parameters were studied in adult rats. Daily administration of the drug caused a significant improvement in the behavioral performance of rats in the active avoidance conditioning test. This effect was observed after about ten days of treatment, and lasted until the end of the experiment (fifteen days). The improvement in this memory-related behavioral test correlated with a facilitation of both muscarinic and beta-adrenergic stimulation of brain adenylyl cyclase activity. Conversely, no changes were observed in basal or forskolin-induced stimulation of cAMP production, suggesting that the alpha-glycerylphosphorylethanolamine effects were not directed on the enzyme itself, but might favor the coupling between receptors, G proteins and effectors. Similar results were observed on the muscarinic stimulation of inositol phosphate accumulation although, in this case, a potentiation of the basal activity also occurred. In conclusion, our data indicate that daily treatment with alpha-glycerylphosphorylethanolamine improves the learning and memory processes in the rat, evaluated using the active avoidance conditioning test. Furthermore, the subchronic administration of this compound is able to enhance receptor-mediated neuronal signal transduction, namely cAMP and inositol phosphate production. These neurochemical modifications may represent, at least in part, the molecular mechanisms of action of the drug.
Florio
T
T
Department of Biomedical Sciences, University of Chieti, Italy.
Bajetto
A
A
Thellung
S
S
Arena
S
S
Corsaro
A
A
Bonavia
R
R
Merlino
M
M
Schettini
G
G
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004789:Enzyme Activation; D005625:Frontal Lobe / Q000201:enzymology / Q000378:metabolism; D007295:Inositol Phosphates / Q000096:biosynthesis; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D000318:Adrenergic beta-Agonists; D018679:Cholinergic Agonists; D007295:Inositol Phosphates; D010714:Phosphatidylethanolamines; C002449:glycerophosphoethanolamine; D002217:Carbachol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol