Age-related changes in hippocampal drug facilitation of memory processing in SAMP8 mice.
SAMP8/TaJf(P8) mouse strain has an inherited age-related impairment of learning and memory, while age-matched subjects of the closely related SAMR1/TaJf(R1) show no impairment. After training on footshock avoidance, P8 and R1 received a drug injection into the hippocampus. Retention was tested 1 week later. The results indicate that bicuculline (GABA antagonist), SKF38393 (DA agonist), and ST587 (NE agonist) facilitated retention with little change in the dose-response curves for P8 mice 4, 8, and 12 months of age. L-glutamate, acting at the NMDA receptor, showed a modest decline in ability to improve retention with increasing age. Arecoline, a muscarinic agonist, had the strongest trend for an age-related decline in potency. The same drug treatments yielded dose-dependent facilitation of retention but no age-related changes in R1 mice. Reduced cholinergic activity in the hippocampus may be, in part, responsible for age-related decline in memory retention in P8 mice.
Flood
J F
JF
Geriatric Research Education and Clinical Center, VA Medical Center, St. Louis, MO 63106, USA.
Harris
F J
FJ
Morley
J E
JE
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains
D018698:Glutamic Acid; D001115:Arecoline; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001640:Bicuculline