THE REINFORCING PROPERTIES OF NICOTINE ARE ASSOCIATED WITH A SPECIFICPATTERNING OF C-FOS EXPRESSION IN THE RAT-BRAIN

Rats were trained for nicotine intravenous infusions in a self-adminis tration paradigm. The effect of nicotine self-administration on region al brain activity was studied by mapping changes of c-fos expression. Specific nicotine effects were determined by comparing the patterning of Fos-like immunoreactivity (Fos-LI) in nicotine self-administering r ats with that in three different control groups. Controls included rat s exposed to the same manipulation as nicotine self-administering rats who received intravenous saline instead of nicotine. In addition, two groups of untrained sham-operated rats exposed daily to the same oper ant boxes were included: one group had the same food restriction used in the operant training, the other was fed ad libitum. Nicotine self-a dministration, exposure to saline and food restriction increased Fos-L I in 43, 33 and three brain regions, respectively, when compared with the control group fed ad libitum. Computer-assisted image analysis of Fos-LI profiles performed on 16 relevant limbic and sensory structures showed that in saline-treated rats a significant (P < 0.01) increase of Fos-LI profiles was observed in medial prefrontal cortex, lateral s eptum, core and ventral shell of nucleus accumbens, claustrum, amygdal oid nuclei, paraventricular thalamic nucleus and lateral geniculate nu cleus. A significant (P < 0.01) further increase produced by nicotine was found in medial prefrontal cortex and ventral shell of nucleus acc umbens. Interestingly, cingulate and piriform cortex, superior collicu lus and medial terminal nucleus of the accessory optic tract were spec ifically activated by nicotine but not saline. These results show that nicotine self-administration activates sensory structures, as well as limbic structures involved in natural rewarding pathways. The results suggest the involvement of restricted terminal regions of the mesocor ticolimbic dopaminergic system in the maintenance of nicotine self-adm inistration.