Much of the addictive power of nicotine in humans may be attributable to learned contextual associations, such that these secondary cues become potent predictive incentives for both maintaining and driving relapse to drug use, even after long periods of abstinence. Here, I review the evidence that chronic nicotine in vivo can induce persistent neuronal changes in excitability within the hippocampal circuitry, with a specific emphasis on the dentate gyrus as an initiator of drug use. The relevance of these early homeostatic (can be fully reversed by acute application of nicotine) neuroadaptations on withdrawal from nicotine is then related to known cognitive deficits also produced following chronic nicotine. I briefly discuss how the hippocampus may influence other parts of the reward circuitry to affect chronic drug use and how periods of drug cessation and/or withdrawal may convert these short-term changes into permanent alterations within the brain that may drive craving and/or relapse many years of abstinence.
©2011 by Walter de Gruyter Berlin Boston