Sc. Pandey et al., Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain, J NEUROCHEM, 77(3), 2001, pp. 943-952
Addiction to nicotine may result in molecular adaptations in the neurocircu
itry of specific brain structures via changes in the cyclic AMP-responsive
element binding protein (CREB)-dependent gene transcription program. We the
refore investigated the effects of chronic nicotine exposure and its withdr
awal on CREB and phosphorylated CREB (p-CREB) protein levels in the rat bra
in. We report here that chronic nicotine exposure (l-h withdrawal) had no e
ffect on the expression of CREB and p-CREB in the rat cortex and amygdala.
On the other hand, decreases in the expression of CREB protein and phosphor
ylation of CREB occur in the cingulate gyrus, and in the parietal and the p
iriform but not in the frontal cortex during nicotine withdrawal (18 h) aft
er nicotine exposure. It was also observed that CREB and p-CREB protein lev
els were significantly decreased in the medial and basolateral, but not in
the central amygdala during nicotine withdrawal (18 h) after chronic nicoti
ne exposure. Furthermore, it was found that nicotine withdrawal (18 h) afte
r chronic nicotine exposure leads to decreased CRE-DNA binding without modu
lating cAMP-dependent protein kinase A activity in the cortex and the amygd
ala of rats. In addition, chronic nicotine treatment produced anxiolytic ef
fects whereas nicotine withdrawal (18 h) produced anxiety in rats as measur
ed by the elevated plus-maze test. These results provide the first evidence
that decreased CREB activity and/or expression in specific cortical and am
ygdaloid brain structures may be involved in the underlying molecular mecha
nisms of nicotine dependence.