Molecular Changes During Protracted Abstinence from Chronic Nicotine
Another mechanism of neuroadaptation that may have long-term consequences includes alterations in gene transcription through changes in the activity of transcription factors. Nicotine exposure, nicotine self-administration, and nicotine withdrawal activate immediate early genes in the ventral tegmental area and projection areas of the mesocorticolimbic dopamine system. Nicotine self-administration and nicotine cues increase Fos-like immunoreactivity in the prefrontal cortex (a marker of neuronal activation). Decreased phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels in the cingulate gyrus, cerebral cortex, medial and basolateral amygdala, and nucleus accumbens have been observed during withdrawal. In rodent studies, decreased CREB in the amygdala during nicotine withdrawal was shown to be correlated with increased anxiety-like responses in the elevated plus maze (Figure 7.26).