[Abstract Title]. - Society for Neuroscience

the hippocampus in vitro (IC50 = 430 nM), revealing a 200-fold lower potency at nAChRs
mediating this response as compared with its potency at nAChR subtypes mediating nicotineevoked
[ 3 H]DA release. The current study sought to determine whether bPiDDB inhibits
nicotine-evoked [ 3 H]NE release through an orthosteric or allosteric mechanism. Also, for the
sake of comparison, the mechanism through which mecamylamine inhibits nicotine-evoked
[ 3 H]NE release was determined. Hippocampal slices were superfused for 60 min with Krebs‟
buffer containing pargyline (a monoamine oxidase inhibitor), and then for 28 min in the absence
or presence of either mecamylamine (100 nM - 10 µM) or bPiDDB (10 nM - 1 µM). Then,
nicotine (1 - 300 µM) was added to the buffer and superfusion continued for an additional 28
min. As expected, mecamylamine-induced inhibition was not overcome by increasing nicotine
concentrations, a result consistent with an allosteric mechanism. bPiDDB also produced
inhibition that could not be surmounted by increasing concentrations of nicotine, and Schild
analysis revealed a linear regression with a slope that was significantly different from 1.0,
suggesting allosteric inhibition. Thus, bPiDDB inhibits nicotine-evoked [ 3 H]NE release in an
allosteric manner, whereas bPiDDB inhibition of nicotine-evoked [ 3 H]DA release is consistent
with an orthosteric mechanism of action. These results support the previous suggestion that
different subtypes of nAChRs mediate these responses, and that bPiDDB inhibits both nAChR
subtypes via different mechanisms. Supported by: NIH Grant U19DA17548 & T32DA007304.
Disclosures: A.M. Smith, None; G. Dhawan, None; Z. Zhang, None; P.A. Crooks, None; L.P.
Dwoskin, None.
Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.13/AA16
Topic: C.16.k. Nicotine
Support: MIUR 2005054943_004
Glaxo research agreement G3166
Title: Chronic nicotine treatment differentially affects the function of presynaptic NMDA
receptors modulating dopamine release from rat prefrontal cortex and nucleus accumbens
Authors: *M. MARCHI 1,2 , M. GRILLI 1 , A. PITTALUGA 1,2 , E. MERLO-PICH 3 ;
1 Dept Exp Med., Pharmacol & Toxicol Sect, Genova 16148, Italy; 2 Ctr. of Excellence for
Biomed. Research, Univ. of Genoa, Genova, Italy; 3 Medicines Res. Ctr., GlaxoSmithKline
S.p.A, Verona, Italy