[Abstract Title]. - Society for Neuroscience

in CB1 KO mice, acute administration of rimonabant (3 mg/kg) ameliorated somatic withdrawal
signs in wild type mice. Increasing endogenous levels of anandamide through genetic or
pharmacological approaches exacerbated the physical somatic signs of spontaneous nicotine
withdrawal in a milder withdrawal model (7-days, 24 mg/kg/day nicotine). Moreover, FAAHcompromised
mice displayed increased conditioned place aversion in a mecamylamineprecipitated
model of nicotine withdrawal. These findings indicate that endocannabinoids play a
role in the rewarding properties of nicotine as well as nicotine dependence liability. Specifically,
increasing endogenous cannabinoid levels magnifies, while disrupting CB1 receptor signaling
attenuates nicotine reward and withdrawal. Collectively, these results support the hypothesis that
cannabinoid receptor antagonists may offer therapeutic advantages to treat tobacco dependence.
Disclosures: P. Patel, None; A. Lichtman, None; B.R. Martin, None; M. Damaj , NIDA DA-
005274 and DA-009789, B. Research Grant (principal investigator, collaborator or consultant
and pending grants as well as grants already received); L. Merritt, None.
Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.4/AA7
Topic: C.16.k. Nicotine
Support: NIH Grant DA-024932
NIH Grant DA-023915
Title: Orexin signaling in the insula regulates nicotine reinforcement
Authors: *J. A. HOLLANDER, P. J. KENNY;
Dept Mol. Therapeut., The Scripps Res. Inst., Jupiter, FL
Abstract: Smokers with damage to the insula have less difficulty quitting the tobacco habit.
Nevertheless, little is known about how this neural substrate modulates tobacco consumption.
Orexin transmission is emerging as a critical regulator of drug seeking, but its role in the
reinforcing effects of nicotine, considered the key addictive component of tobacco, is unclear.
We found that the selective orexin-1 receptor antagonist SB-334867 (0.5-6 mg/kg IP) dosedependently
attenuated the lowering effects of nicotine (0.25 mg/kg SC) on intracranial selfstimulation
(ICSS) thresholds in rats, considered a measure of the stimulatory effects of nicotine
on brain reward systems that that may motivate nicotine consumption. In addition, we found that
SB-334867 (0.5-4 mg/kg IP) dose-dependently decreased responding for intravenous nicotine