Facilitation of glutamate receptors reverses an age-associated memory impairment in rats

The accuracy of memory for recent events is reported to decay between young adulthood and middle age in humans (Crook et al., 1990; Crook and West, 1990; Thomas et al., 1977) due to impairments in acquisition and/or retention (Craik, 1977; Huppert and Kopelman, 1989). Effects of this kind are also found in comparisons of middle-aged (12-18 months) vs. young adult (3 months) rats in tests requiring retention of recently sampled spatial cues (Kadar et al., 1990a; Kadar et al., 1990b; Goudsmit et al., 1990; Weiss and Thompson, 1991). The causes of such changes in memory processing are unknown but might be expected to involve age-related losses in forebrain glutamate receptors (Bahr et al., 1992; Magnusson and Cotman, 1993; Wenk et al., 1991); these receptors mediate fast excitatory transmission in many brain regions and play an essential role in the production of long-term potentiation (LTP), a form of synaptic plasticity that has been implicated in memory encoding (Landfield and Lynch, 1977; Moore et al., 1993). In the present communication we report results indicating that a drug that enhances AMPA-type glutamate receptors acts centrally to selectively increase hippocampal spatial cell firing and improves both acquisition performance and memory retention in middle-aged rats to levels equivalent to those found in young adult animals.