The pronounced effect of PTSD co-morbidity on nicotine withdrawal suggests that stress reactivity pathways are central to the negative effects that occur during nicotine withdrawal. Stress hormones modulate the activity of neurotransmitter systems in brain regions that are essential for the development and maintenance of addiction to nicotine and other substances. For example, stress hormones alter dopaminergic activity in the ventral tegmentum44 and the nucleus accumbens (NAcc).45 The activity of stress hormones in the NAcc may contribute to the withdrawal effects of nicotine. Marcinkiewcz et al. found that blocking CRF signaling specifically in the NAcc reduced nicotine withdrawal in rats.46
