[Abstract Title]. - Society for Neuroscience

Poster
258. Molecular and Neurochemical Basis of Nicotine Addiction
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 258.11/AA14
Topic: C.16.k. Nicotine
Support: NIH Grant DA-021801
Title: Topographically patterned influence of acute nicotine on serotonin and GABA in the
ascending raphe nuclei
Authors: *R. E. SPERLING 1,2 , K. G. COMMONS 1,2 ;
1 Anesthesia, Children's Hosp Boston, Boston, MA; 2 Harvard Med. Sch., Boston, MA
Abstract: Studies have shown that chronic nicotine reduces anxiety while nicotine
withdrawal is anxiogenic. The serotonergic system has been implicated in
mediating these effects, specifically neurons from the dorsal raphe nucleus
(DR) and median raphe (MR), which project to areas in the forebrain
responsible for controlling anxiety state. Previous studies have reported
that acute nicotine produces an oscillatory increase of serotonin (5-HT) and
GABAergic neuronal activity within the DR. Moreover, 5-HT-1A receptors may
play a role directing 5-HT cell activity during nicotine exposure. The aim
of the present study was to establish the topography of 5-HT and GABA
neurons in the DR and MR that are activated in response to acute nicotine
administration as measured by Fos immunoreactivity. In addition, we
examined the role of 5-HT-1A receptors in controlling Fos activation
specifically in 5-HT cells. Adult male Sprague-Dawley rats received a
single dose of nicotine (0.2-0.8 mg/kg) or saline. Tissue sections through
the MR and DR were processed for dual immunolabeling of Fos and either 5-HT
or GABA. Acute nicotine injections resulted in a moderate increase in Fos
expression in 5-HT neurons that was most pronounced in the rostral-dorsal
DR. Immunolabeling of Fos with GABA identified many dually labeled cells,
predominantly in the rostral DR, as well as laterally. To determine if Fos
expression in 5-HT cells was dampened by 5-HT-1A-dependent processes, we
assayed the effect of the 5-HT-1A receptor antagonist (WAY-100635, 0.1
mg/kg) in nicotine (0.4 mg/kg) and saline treated rats. Nicotine in
combination with WAY-100635 produced a notable increase in Fos activation in
5-HT cells in the dorsal DR. This effect peaked rostrally and, while
remaining dorsal, extended through the caudal DR. The results of the