[Abstract Title]. - Society for Neuroscience

infusions (0.03 mg/kg/infusion) but not for food rewards (45 mg) under fixed and progressive
ratio schedules of reinforcement. These data suggest that orexin transmission plays a central role
in regulating the stimulatory effects of nicotine on brain reward systems, and thereby controls the
motivation to consume the drug. Finally, we found that infusion of SB-334867 (.04-5 microg)
directly into the insula decreased intravenous nicotine self-administration (0.03 mg/kg/infusion)
under a fixed ratio schedule. As such, these findings suggest that insular orexin transmission may
represent a critical substrate necessary for maintaining tobacco dependence.
Disclosures: J.A. Hollander , None; P.J. Kenny, None.
Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.5/AA8
Topic: C.16.k. Nicotine
Support: NIH Grant DA024330
Title: Cyclic GMP-dependent protein kinase type II contributes to nicotine cue reactivity in mice
Authors: *D. SCOTT 1 , M. LEE 2 , F. HOFMANN 3 , N. HIROI 1,2 ;
1 Dominick P. Purpura Dept Neurosc, 2 Psychiatry and Behavioral Sci., Albert Einstein Coll.
Med., Bronx, NY; 3 Inst. für Pharmakologie und Toxicologie, Technische Univ. München,
Munich, Germany
Abstract: Cues associated with smoking and withdrawal contribute to persistent smoking in
smokers and relapses in ex-smokers. However, because the molecular mechanisms underlying
cue reactivity are still poorly understood, effective treatment to extinguish the impact of cues is
not available. We have previously observed that a single nicotine injection up-regulated cGMPdependent
protein kinase (cGK) activity in the amygdala and caudate-putamen of adolescent
mice, and in the nucleus accumbens and ventral tegmental area of adult mice. We have now
examined the role of cGK type II (cGKII) in approach behavior toward cues associated with
nicotine and in avoidance triggered by cues associated with precipitated withdrawal in the place
conditioning paradigm. Congenic cGKII wild-type (WT), heterozygous (HT), and knockout
(KO) mice were repeatedly tested for expression of conditioned place preference (CPP)
following a single pairing of nicotine (0.2 mg free base/kg, s.c.). WT mice showed potentiation
of CPP during the first 4 nicotine-free test days and extinction thereafter, but KO mice exhibited
complete extinction by the second test; HT mice showed an intermediate trend. We have now
begun examining the role of cGKII in avoidance triggered by cues associated with withdrawal.