A profile of the behavioral changes produced by facilitation of AMPA-type glutamate receptors
by
Davis CM, Moskovitz B, Nguyen MA,
Tran BB, Arai A, Lynch G, Granger R.
Center for the Neurobiology of Learning and Memory,
University of California, Irvine 92697-3800, USA
Psychopharmacology (Berl) 1997 Sep;133(2):161-7
ABSTRACT
A newly developed group of benzoylpiperidine drugs
that enhance AMPA-receptor-gated currents ("ampakines") has been shown to
improve memory encoding in rats across a variety of experimental paradigms.
The present experiments were intended to i) provide a partial profile of
the behavioral changes produced by ampakines, ii) test if two ampakines
(BDP-12 and BDP-20) that differ significantly in their effects on AMPA receptor
kinetics produce similar behavioral profiles, and iii) determine if physiological
potency is reflected in behavioral potency. BDP-20 reduced two measures
of exploratory activity in aged rats but increased speed of performance
in a radial maze; the drug also caused substantially improved retention
of spatial information. These results are similar to those obtained with
BDP-12, an analog that differs from BDP-20 in its effects on ligand binding
to the AMPA receptor and on the physiological responses of the receptors
to glutamate. BDP-20 was approximately ten-fold more potent in behavioral
effects than BDP-12, which agrees with the relative potencies of the two
drugs as assessed with excised patches and excitatory synaptic responses.
These findings indicate that ampakines, though differing in their effects
on AMPA-receptor-mediated responses, have similar effects at the behavioral
level.
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