[Abstract Title]. - Society for Neuroscience

that will require further investigation. The observed changes in neurotrophic and inflammatory
hippocampal milieu are compelling candidate mechanisms for prenatal choline
supplementation‟s preservation of cognitive performance with old age.
Disclosures: M.J. Glenn, None; S.D. Bilbo, None; C.L. Williams , None; T.J. Mellott,
None; J.K. Blusztajn, None.
Poster
290. Animal Cognition and Behavior: Learning and Memory: Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 290.19/RR70
Topic: F.02.j. Learning and memory: Pharmacology
Support: Abbott Laboratories
NIH Grant KO2 MH01072
NIH grant MH080332
Title: nAChR agonist-evoked glutamatergic and cholinergic transients in the prefrontal cortex of
mice lacking the beta2- or alpha7-nAChR receptor subunit
Authors: *J. JI 1 , V. PARIKH 1 , M. W. DECKER 2 , M. SARTER 1 ;
1 Dept Psychol, Univ. of Michigan, Ann Arbor, MI; 2 Neurosci. Drug Discovery, Abbott Labs.,
Abbott Parik, IL
Abstract: Increases in cortical cholinergic activity mediate the pro-cognitive effects of nAChR
agonists. Recently, we demonstrated in rats that the amplitudes of cholinergic transients that are
evoked by nAChR agonists are mediated via glutamatergic transients and NMDA and AMPA
receptor stimulation. Furthermore, compared to the effects of nicotine, the α4β2-selective
nAChR partial agonist ABT-089, which has demonstrated efficacy in a small ADHD trial, was
more potent in eliciting glutamatergic and cholinergic transients. Additionally, the cholinergic
transients evoked by ABT-089 lacked the slow decay rate of nicotine-evoked transients. To
substantiate the neuropharmacological model derived from these experiments, cholinergic and
glutamatergic transients were measured following local pressure ejections of nicotine and ABT-
089 into the prefrontal cortex of mice lacking the β2- or α7-subunit of the nAChR. Similar to
results in rats, in wild-type (WT) mice, cholinergic signal amplitudes following ABT-089 (10
pmol-2.5 nmol) were characterized by more potent signal amplitudes and faster decay rates when
compared with the effects of nicotine (10 pmol-2.5 nmol). In β2 knock-out (KO) mice, nicotine-