This review has summarized multiple different mechanisms that underlie persistent, long-lasting changes in synaptic efficacy following administration of addictive drugs. It is becoming more and more evident that nicotinic receptors significantly facilitate the induction and maintenance of plasticity—including LTP, LTD, and structural changes—in the hippocampus, amygdala, and mesolimbic dopaminergic system, thus contributing to the molecular underpinnings of nicotine and alcohol addiction. Nicotine exerts its powerful effects by a dynamic, parallel activation, and desensitization of nAChRs. Up-regulation of nAChRs following nicotine treatment reflects a compensatory response to excessive receptor stimulation, and there is compelling experimental evidence to suggest this plays a major part in nicotine dependence. Although few studies have addressed ethanol-induced synaptic plasticity via interactions with nicotinic receptors, ethanol undoubtedly potentiates nAChR currents and drugs targeting nAChRs can attenuate voluntary alcohol consumption in both rodents and humans. Importantly, there is a need to understand the molecular and cellular ramifications of co-administration of nicotine and ethanol due to the high comorbidity of these substances in human addicts. Future studies should aim to unravel the common neural mechanisms shared by these two
