Administration of drugs activating
cannabinoid CB(1) receptors in the brain induces
memory deficit in rodents, and blockade of these receptors may restore memory capacity in these animals. Central administration of
beta-amyloid or
beta-amyloid fragments may also lead to memory disturbances. This study was undertaken to study the involvement of
cannabinoid CB(1) receptors in
amnesia induced by
beta-amyloid fragments in mice tested in a step-through passive avoidance paradigm. Pre-training intracerebroventricular (i.c.v.) injection of
beta-amyloid fragments,
beta-amyloid peptide-(25-35) (4, 8 or 16 nmol/mouse) or
beta-amyloid peptide-(1-42) (200, 400, 800 pmol/mouse) 7 days prior to the learning trial reduced in a dose-dependent manner the retention of passive avoidance response. This effect was observed in two retention tests, 1 and 7 days after the learning trial. The two
beta-amyloid fragments showed similar potency in reducing retention of passive avoidance behavior. This effect was counteracted by a single intraperitoneal (i.p.) injection of the
cannabinoid CB(1) receptor antagonist, N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (
SR141716A, 1 mg/kg), made 30 min prior to the second retention test. The injection of
SR141716A per se did not affect memory capacity of mice. The i.c.v. administration of
beta-amyloid peptide-(25-35) (8 nmol/mouse) or of
beta-amyloid peptide-(1-42) (400 pmol/mouse) made 30 min prior to the learning trial failed to affect the retention capacity of mice as measured 1 and 7 days later. Also, the i.p. injection of
SR 141716A (1 mg/kg) made 30 min prior to the learning trial did not influence the behavioral response of mice injected with
beta-amyloid peptide-(25-35) (8 nmol/mouse) or of
beta-amyloid peptide-(1-42) (400 pmol/mouse) 7 days prior to the learning trial. These results show that
beta-amyloid fragments induce a dose-dependent
memory deficit. Their effect on memory retention depends upon the time of administration and seems to involve
cannabinoid CB(1) receptors in the brain.