Within-subject memory decline in middle-aged rats: effects of intraseptal tacrine

Neurobiol Aging. 2004 Oct;25(9):1221-9. doi: 10.1016/j.neurobiolaging.2003.12.006.

Abstract

A longitudinal design was used to examine spatial working memory performance in aging Long-Evans rats on a 12-arm, delayed-non-match-to-sample radial maze task. Compared to performance at 12-13 months of age, the same rats exhibited a significant performance deficit at 15-16 months of age across all retention intervals (1.5-10h). All rats exhibited some degree of decline, and no rat performed as well as they had 3 months earlier. This early onset deficit may relate to the degree of difficulty required to perform accurately in a task that maximizes both spatial information processing and flexible working memory representations. Following our observation, rats were implanted with a chronic cannula aimed at the medial septal nucleus. Acute intraseptal tacrine treatments (0.0-25 micrograms/0.5 microl) did not significantly affect any index of performance. Rats exhibited further memory decline over the course of testing (up to 20 months of age). Detection of early onset dysfunction could allow for experimental analysis of underlying mechanisms and therapeutic strategies early in the course of age-related changes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Aging / physiology
  • Animals
  • Catheterization
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism
  • Drug Administration Routes
  • Early Diagnosis
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Nootropic Agents / pharmacology
  • Rats
  • Rats, Long-Evans
  • Septal Nuclei / drug effects
  • Septal Nuclei / physiopathology
  • Septum of Brain / drug effects*
  • Septum of Brain / physiopathology
  • Tacrine / pharmacology*
  • Tacrine / therapeutic use
  • Treatment Failure
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Nootropic Agents
  • Tacrine
  • gamma-Aminobutyric Acid
  • Acetylcholine