ADMINISTRATION OF AMYLOID BETA-PEPTIDES IN THE RAT MEDIAL SEPTUM CAUSES MEMORY DEFICITS - REVERSAL BY SR 57746A, A NONPEPTIDE NEUROTROPHIC COMPOUND

Different putative toxic amyloid beta (A beta) peptides, beta(1-40), b eta(1-40) and beta(25-35), were infused (0.75, 1.5 or 3 nmol) in the r at medial septum. Memory deficits were then investigated using the soc ial recognition test. A significant amnesia was observed 4, 7 and 14 d ays after intraseptal injection of 3 nmol of beta(1-42), beta(1-40) an d beta(25-35). Lower amounts of beta(1-42) were inactive except 1.5 nm ol that disrupted memory 7 days post-treatment. Used as control, the i nverted peptide beta(40-1) and the scrambled beta(25-35) were inactive . rising the prolongation procedure, rats infused with 3 nmol of beta( 1-40) were still able to recognize the same juvenile. Finally, a daily treatment with the non-peptide neurotrophic compound SR 57746A (10 mg /kg p.o.) over 21 days, prevented the deficits in short-term memory in duced by the intraseptal infusion of 3 nmol of either beta(1-40) or be ta(25-35). These findings suggest that A beta fragments could impair s hort-term memory when infused in the rat medial septum, an effect that is prevented by SR 57746A.