Title: EFFECT OF DSERINE ON A CUEPLACE COMPETITION TEST IN THE WATER MAZE
1College of Liberal Arts
EFFECT OF D-SERINE ON A CUE-PLACE COMPETITION
TEST IN THE WATER MAZE
J. Josiah Horton, Marshall G. Miller, Allison H.
ONeill, Kevin A. Strubler, Jacqueline A.
Vasinda
Faculty Sponsor Bryan D. Devan Psychology
Department
Abstract Previous research has suggested that
systemic administration of D-serine may
strengthen the consolidation of information
learned the preceding day. Twenty-three
Long-Evans hooded rats were trained in the Morris
water maze. They were then divided into groups
that were given either D-serine or saline,
followed by a cue-place competition test. The
results of the first part of this study revealed
no significant difference in performance when the
rats were only administered D-serine the day of
the competition test. In the second part of the
study a significant difference in performance was
found the day following the administration.
Furthermore, this difference was also present
after a ten day retention period. This suggests
that D-serine enhances memory acquisition and
retention, rather than effecting retrieval.
Background Behavioral pharmacological evidence
suggests that the glutamatergic
N-methyl-D-aspartate (NMDA) receptor complex
plays an important role in learning and memory.
Consequently, this neurotransmitter receptor site
is a target in the search for cognitive enhancers
to treat age-related memory decline. It was
recently found that the amino acid D-serine is an
endogenous co-transmitter at the glycine
recognition site of the NMDA receptor (see Figure
1). Previous research from our lab shows that
D-serine enhances spatial win-stay behavior in
the water maze, suggesting a possible enhancement
of spatial memory consolidation.
Figures 1. Diagram of the NMDA receptor complex
with recognition sites that modulate channel
function, including the two co transmitter sites
for glutamate and D-serine. Signal transduction
following receptor activation and potential
retrograde signaling by nitric oxide are also
shown.
2Specific Aims To determine whether D-serine would
enhance the retrieval of information about the
location of a platform in the Morris Water
Maze. Hypothesis 1 Rats who were administered
D-serine will search more rigorously in the
trained location (where the platform was during
acquisition) than the control group during a
competition test. Hypothesis 2 D-serine will
improve memory of the preceding days learning
during a retention test.
- Methods
- Subjects 23 Long-Evans hooded rats
- Morris water maze The Morris water maze consists
of a - 166cm diameter pool containing water clouded with
white - non-toxic tempera paint. After being released at
one of four - pseudorandomly selected start points (N, E, S, W)
along the - pools perimeter, rats must locate the platform
in order to escape. - Acquisition phase (Days 1-12) During
acquisition, the platform is underwater (hidden)
25 of the time, and above water (visible) 75 of
the time. The location of the platform is always
in the center of the Northeast quadrant. - Competition test (Day 13) Subjects were
administered either D-serine or saline via
intraperitoneal injection 40 minutes prior to
testing. During the competition test, the
platform is visible but it is moved to the
Southwest quadrant. - Post-competition test (Day 14) During the
post-competition test, the platform remains in
the Southwest quadrant but is hidden. - Probe test (Day 23) No platform is present
during the probe test.
Figure 2. Diagram of the water maze. XAnnulus,
OPlatform
Figure 3. Photograph of the water maze on a
visible platform day.
- Results
- Acquisition Subjects in both groups acquired
- place information at approximately the same
- rate (Fig. 4) with no significant differences.
- 2. Competition Test
- There were no significant differences between
groups - on measures of escape latency, percent of time
or - distance traveled in Northeast quadrant, number
of - passes through Northeast counter, or latency to
enter - Northeast or Southwest counter.
- (counter 4x platform diameter)
- 3. Post-Competition Test
- Significant difference between groups
- Latency to Enter Counter - New Location
- F(1,21) 6.654, p lt .05
- Number of Passes Through Counter - New Location
- F(1,21) 8.451, p lt .05
Figure 4. The mean escape latency by group during
the acquisition phase. Days 4, 8, 12 use a
hidden platform.
Figures 5. Examples of swim paths.
3Discussion The results of the first part of the
study revealed no significant differences in
performance when the rats were administered
D-serine the day of the competition test.. A
significant enhancement in performance was found
the following day. Furthermore, this difference
was also present after a ten day retention
period. This suggests that D-serine enhances the
consolidation of recent cognitive-spatial memory
rather than affecting retrieval of previous place
learning. The present findings provide
preclinical support for further investigation of
D-serines ability to selectively enhance some
aspects of cognitive-spatial memory.
References Mothet, J. P., Parent, A. T.,
Wolosker, H., Brady, R. O., Linden, D. J.,
Ferris, C. D., et al. (2000). D-Serine is an
endogenous ligand for the glycine site of the
N-methyl-D-aspartate receptor. Proceedings
National Academy of Science USA, 97,
4926-4931. Purves, D., Augustine, G. J.,
Fitzpatrick, D., Hall, W. C., LaMantia, A.,
McNamara, J. O., et al. (2004). Neurosignaling
Neurotransmitters, receptors and their effects.
In G. J. Augustine (Ed.), Neuroscience (Third
edition). Sunderland, MA Sinauer Associates,
Inc. Rao, T. S., Cler, J. A., Emmett, M. R.,
Mick, S. J., Iyengar, S., Wood, P. L. (1990).
Glycine, glycinamide, and D-serine act as
positive modulators of signal transduction at
the N-methyl-D-aspartate (NMDA) receptor in vivo
Differential effects on mouse cerebellar cyclic
guanosine monophosphate levels.
Neuropharmacology, 29, 1075-1080. Stouffer, E.
M., Petri, H. L., Devan, B. D. (2004). Short
communication Effect of D-Serine on a delayed
match to place task. Behavioral Brain Research,
152, 447-452. Wake, K., Yamazaki, H., Hanzawa,
S., Konno, R., Sakio, H., Niwa, A., et al.
(2001). Exaggerated responses to nosiceptive
stimuli and enhancement of N-methyl-D-aspartate
(NMDA) receptor mediated synaptic transmission in
mutant mice lacking D-amino-acid Oxidase.
Neuroscience Letters, 297, 25-28. Wroblewski, J.
T., Fadda, E., Mazetta, J., Lazarewicz, J. W.,
Costa, E. (1989). Glycine and D- serine act as
positive modulators of signal transduction at
N-methyl-D-aspartate sensitive glutamate
receptors in cultured cerebellar granule cells.
Neuropharmacology, 28, 447-452.