[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 291.29/SS12
Topic: F.02.j. Learning and memory: Pharmacology
Support: Abbott Laboratories
Title: Improvement of sensory gating by the histamine H3 antagonist ABT-239 is blocked by the
muscarinic antagonist scopolamine
Authors: *H. ROBB, R. S. BITNER, J. D. BRIONI, R. J. RADEK;
Neurosci. Res., Abbott Labs, Abbott Park, IL
Abstract: ABT-239 is an H3 receptor antagonist that improves sensory gating in DBA/2 mice.
Gating is a processing function of the CNS that filters redundant sensory information and is
deficient in schizophrenic patients. H3 antagonists increase extracellular histamine and
acetylcholine (ACh), which may mediate the effects of ABT-239 on sensory gating. To
investigate this, we attempted to block the effects of ABT-239 on sensory gating in mice with
antagonists of histamine and ACh receptors. Sensory gating was assessed by recording
hippocampal evoked potential (EP) EEG in freely moving DBA/2 mice. EPs were elicited with
pairs of auditory clicks, and gating ratios were calculated by dividing the amplitude of the second
EP (click 2) by the amplitude of the first EP (click 1). In the first study, the histamine H1 receptor
antagonist diphenhydramine (10.0 mg base/kg) failed to block the effect of ABT-239 (3.0 mg/kg
i.p.) to lower gating ratio and improve gating. An ACh receptor mechanism was investigated by
pretreating animals with either the nicotinic ACh receptor antagonist mecamylamine (MEC, 5.0
κmol/kg), or the muscarinic ACh receptor antagonist scopolamine (SCOP, 1.0 mg base/kg).
SCOP, but not MEC, blocked the effects of ABT-239 to improve gating. In summary, these
studies suggest that the effect of ABT-239 on sensory gating is mediated by muscarinic ACh
receptors, but not nicotinic ACh or histamine H1 receptors.
Disclosures: H. Robb, Abbott Laboratories, A. Employment (full or part-time); R.S. Bitner,
Abbott Laboratories, A. Employment (full or part-time); J.D. Brioni, Abbott Laboratories, A.
Employment (full or part-time); R.J. Radek, Abbott Laboratories, A. Employment (full or parttime).
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 291.30/SS13
Topic: F.02.j. Learning and memory: Pharmacology