Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats

Abstract

Exposures to uncontrollable stress have been shown to alter ensuing synaptic plasticity in the hippocampus and interfere with hippocampal-dependent spatial memory in rats. The present study examined whether stress, which impairs hippocampal long-term potentiation (LTP), also affects (nonspatial) hippocampal-dependent object-recognition memory, as tested on the visual paired comparison task (VPC) in rats. After undergoing an inescapable restraint-tailshock stress experience, rats exhibited markedly impaired recognition memory at the 3-h (long) familiarization-to-test phase delay but not at the 5-min (short) delay. In contrast, unstressed control animals showed robust recognition memory (i.e., they exhibited reliable preferences for novel over familiar objects) at both short- and long-delay periods. The impairing effect of stress on long-delay recognition memory was transient because 48 h after undergoing stress experience, animals performed normally at the long delay. Similar to stress, microinfusions of DL-2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate receptor (NMDAR) antagonist that blocks LTP, into the dorsal hippocampus selectively impaired object-recognition memory at the long-delay period. Together, these results suggest that stress and intrahippocampal administration of APV affect recognition memory by influencing synaptic plasticity in the hippocampus.

Figure 1

(A) Mean time in seconds (+S.E.) control-5 min and stress-5 min animals spent exploring (left panel) two identical objects (unshaded bars) during the familiarization phase, and (right panel) 5 min later one novel object (shaded bars) and one previously explored, familiar (unshaded bars) object during the test phase. (B) Mean time in seconds (+S.E.) control-3 h, stress-3 h, and 48-h poststress-3 hr animals spent exploring (left panel) two identical objects (unshaded bars) during the familiarization phase and (right panel) 3 h later one novel object (shaded bars) and one previously explored (unshaded bars) object during the test phase. Asterisk denotes statistical significance.

Figure 2

Effects of restrain–tailshock stress on Schaffer collateral/commissural-CA1 long-term potentiation. Synaptic strength in the CA1 area of the hippocampus from control (open circles; n = 6) and stress (filled circles; n = 6) is expressed as a percentage of the average pretetanus field excitatory postsynaptic potentials (f-EPSP) over time (in minutes).

Figure 3

Location of injection sites based on a reconstruction of guide cannulae placements in the dorsal hippocampus from 5-min (left panel) and 3-h (right panel) groups of rats.

Figure 4

(A) Mean time (+S.E.) ACSF-5 min and APV-5 min animals spent exploring (left panel) two identical objects during the familiarization phase and (right panel) 5 min later one novel object and one familiar object during the test phase. (B) Mean time (+S.E.) ACSF-3 h and APV-3 h animals spent exploring (left panel) two identical objects during the familiarization phase and (right panel) 3 h later one novel object and one familiar object during the test phase.