[Abstract Title]. - Society for Neuroscience

from young rats in order to clarify the mechanism underlying its procognitive effect.
Application of ACh in the presence of atropine and physostigmine immediately increased the
frequency of spontaneous postsynaptic currents (sPSCs) recorded in CA1 pyramidal neurons.
ZSET1446 significantly potentiated this facilitatory effect of ACh with a maximum effect at a
concentration of 100 pM (range tested, 10 pM - 1 nM), suggesting a bell-shaped dose-response
relation. Such potentiation with ZSET1446 was observed both in the pharmacological isolation
of inhibitory and excitatory sPSCs and also either in the pharmacological blockade of alpha7 or
alpha4beta2 nAChRs. It is unlikely that this potentiation resulted from the effect on spontaneous
transmission because the sPSC frequency before ACh application was not significantly affected
by ZSET1446. ACh-activated inward current and ACh-induced depolarization of interneurons in
the stratum radiatum and lucunosum-moleculare were not significantly affected by ZSET1446,
suggesting modulation of the ACh-mediated excitation of interneurons does not underlie the
potentiation by ZSET1446. These results indicate that ZSET1446 potentiates the nicotinemediated
enhancement of synaptic transmission in the hippocampal neurons, without affecting
nAChRs themselves, providing a novel possible mechanism of procognitive action that might
partly underlie the improvement of the learning deficit in animal models of AD.
Disclosures: K. Takeda, Zenyaku Kogyo Co, Ltd, A. Employment (full or part-time); Y.
Yamaguchi , Zenyaku Kogyo Co, Ltd, A. Employment (full or part-time); M. Hino, Zenyaku
Kogyo Co, Ltd, A. Employment (full or part-time); F. Kato, None.
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 291.5/RR80
Topic: F.02.j. Learning and memory: Pharmacology
Title: Behavioral phenotyping of mice knockout for the sigma-1 chaperone protein (Oprs1-/-)
revealed sex-related memory deficits
Authors: *T. MAURICE, F. MALHAIRE, N. CHEVALLIER;
INSERM U.710, Montpellier, France
Abstract: The sigma-1 receptor (S1R) is an intracellular neuromodulatory protein newly
identified as an endoplasmic reticulum (ER)/mitochondrion interface-associated chaperone (Su
& Hayashi, 2007, Cell 131:596). It regulates Ca2+ mobilization through IP3 receptors and cross
activates other ER resident chaperones like Grp78/Bip. S1R therefore facilitates activitydependent
signaling and several compounds selectively target S1R, thus appearing as a unique
ligand-operated chaperone. S1R ligands are anti-amnesic, antidepressant, anti-addictive and