tegmental area and the shell of the nucleus acumbens). Following repeated exposure, the nicotinic acetylcholine receptors adapt to nicotine and become unresponsive. It is hypothesized that the reactivation of these closed receptors following abstinence/cessation gives rise to symptoms of craving and withdrawal which, in turn, reinforce continuing smoking/relapse. We implicated in quantity smoked and ever smoking pathways relating to the Anaphase-Promoting Complex/Cyclosome mediated degradation of Cdc20 and other APC/CCdh1-targeted proteins. Although none of these pathways was associated with both smoking phenotypes, they are inter-connected, forming chains of pathways governing different stages of cell division. These pathways control not only the mitotic regulators of DNA replication (i.e., APCCdc20) but also axon growth and synaptic plasticity (i.e., APCCdh1) 45; hence our results lend support to the idea that neuronal plasticity and learning play a paramount role in the development of nicotine addiction 43. Furthermore, for the cell-cycle pathways are known to belong to ‘a subway map of cancer pathways’ 46 given their role in cancer development (a disease of unregulated cell proliferation), our results suggest that some of the same biological mechanisms underlie both smoking and cancer, as first conjectured by Fisher47: “[…] cigarette smoking and lung cancer, though not mutually causative,
