Nicotinic acetylcholine receptors (nAChRs) mediate the physiological effects of exogenous nicotine. They also play critical physiological roles throughout the brain and body by mediating cholinergic excitatory neurotransmission, modulating the release of neurotransmitters, and having longer-term effects on gene expression and cellular connections¹.

nAChRs are pentameric complexes made up of combinations of a number of different nAChR subunits, which can be classified as α subunits and non-α subunits (‘structural’ subunits), which can be defined as β subunits when they are expressed in the vertebrate nervous system². There are nine α subunits (α2-α10) and three β subunits (β2, β3, and β4) in the CNS³. Nicotinic receptors are assembled as combinations of α (2-6) and β (2-4) subunits. 

All α subunits are expressed in neuronal cells except for the α1 subunit which is specifically expressed in skeletal muscle. They are also expressed in non-neuronal cells such as bronchial epithelial cells⁴, as well lymphocytes⁵. In the CNS, the α5 subunit is widely expressed in the CA1 area of the hippocampus which affects learning, memory, attention, anxiety, and potentially drug seeking behaviors.

Nicotinic acetylcholine receptor α5 is associated with different aspects of smoking behavior as well as with smoking related disorders. In addition, it has been found to be upregulated in smokers or differentially expressed in lung tumor cells⁶.