Nicotinic receptors are localized both pre- and post-synaptically where agonist-induced cation influx results in membrane depolarization and/or CA2+-dependent signaling cascades, thereby regulating neuronal excitability and neurotransmitter release (Albuquerque et al., 1995). nAChRs play a significant role in modulating glutamatergic, GABAergic, and dopaminergic neurotransmission in the mesolimbic pathway (Blomqvist et al., 1992; Caille et al., 2009; Mao et al., 2011), thus contributing to the rewarding effects of drugs of abuse and synaptic plasticity in this system as well as in other brain regions such as the hippocampus and amygdala (Ericson et al., 2009; Hendrickson et al., 2010; Reperant et al., 2010). Moreover upon exposure to nicotine and ethanol, nicotinic receptors can undergo changes in expression (stoichiometries or receptor number) and function which may underlie aspects of physical dependence and withdrawal symptoms (Nashmi et al., 2007). Since the majority of alcoholics are also smokers, determining the coincident molecular underpinnings in the development of their dependence may be useful in treating these addictions.
