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Journal of Neuroscience, Vol 15, 8023-8030, Copyright © 1995 by Society for Neuroscience
Facilitation of olfactory learning by a modulator of AMPA receptors
J Larson, T Lieu, V Petchpradub, B LeDuc, H Ngo, GA Rogers and G Lynch
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717-3800, USA.
The effects of a benzoyl-piperidine drug (BDP) that facilitates AMPA
receptor-mediated synaptic responses were tested on the acquisition and
retention of long-term memory at dosages that had no detectable effects on
a variety of performance measures. BDP-12 produced a dose-dependent
suppression of exploratory activity in rats with statistically reliable
effects occurring at 50 mg/kg (i.p.). The drug had no effects on balance
beam performance at 30 mg/kg but at 45 mg/kg reduced the number of
crossings made within a session; it did not, however, affect the time
required to perform a traversal. The performance of well-trained rats
presented with a familiar pair of odors (correct and incorrect) was not not
detectably altered by BDP-12 at 30 mg/kg; however, the number of correct
responses made in a five-trial test was reduced at 45 mg/kg. These results
indicate that the AMPA receptor modulator at 30 mg/kg has little influence
on arousal, motivation, sensori-motor processing, and attention; higher
dosages cause a depression of learned and unlearned prepotent responses.
The effects of the lower concentration were tested on two-odor
discrimination learning in rats that had extensive training on the task.
The animals (n = 20) were given three or five acquisition trials with novel
odor pairs immediately after an injection of drug or vehicle and then
tested 1-3 d later for retention in five unrewarded probe trials. Retention
performance was not significantly better than chance 52.6 +/- 4.5% correct)
for odors learned on vehicle injection days but was well above chance for
odors learned on drug injection days (70.6 +/- 4.2% correct).
Within-subject comparisons confirmed the memory enhancing effect of BDP-12
(p < 0.01). Analyses of performance during five training trials
indicated that the rats made more correct responses on days on which they
were given the drug than on days on which they were injected with vehicle
(p < 0.02). Within-subject differences in acquisition were correlated
with differences in retention (r = 0.70). There were no evident effects of
the drug on response latencies during acquisition. These results suggest
that AMPA receptor modulators reduce the amount of training needed for the
formation of long-term memory and do so at dosages which have little effect
on variables that secondarily influence acquisition. Possible reasons for
this selectivity are discussed.
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