Table 2.

Main findings in nAChR mutant KO mice.

Deleted Gene	Critical Phenotype in nAChR Null Mutant Mice	Refs.
CHRNA2	Increased self-administration; no somatic signs and hyperalgesia with conditioned CPA; context-dependent nicotine abstinence	[174, 210, 211]
CHRNA4	More hypersensitive to nicotine than the wild-type; increased basal anxiety (EPM); blunted basal level and nicotine-stimulated DA release.	[184, 197-200]
CHRNA5	Increased nicotine intake and self-administration; enhanced anxiety during nicotine withdrawal; reduced somatic symptoms; no signs of hyperalgesia or anhedonia.	[109, 174, 176-179]
CHRNA6	Blocked nicotine withdrawal-induced CPA and anxiety; nicotine self-administration blocked; blunted nicotine-stimulated DA release; reduced anxiety and aversion in pharmacological blockade.	[186, 189-193]
CHRNA7	Unaffected anxiety-like behavior; unaffected nicotine self-administration; increased nicotine-stimulated DA release; blunted nicotine self-administration; delayed onset of nicotine withdrawal-induced anhedonia-like behavior; significantly reduced chronic oral nicotine intake and nicotine withdrawal-induced somatic symptoms.	[109, 182, 213-216]
CHRNB2	No somatic signs and abstinence-induced hyperalgesia; no nicotine-stimulated DAergic neuron firing; no anxiety or anxiety-related behavior (EPM); blocked nicotine-evoked DA release; blocked nicotine self-administration and conditioned reinforcement.	[109, 110, 201-206]
CHRNB3	Decreased anxiety (EPM); altered hypothalamic pituitary–adrenal axis responses; altered locomotor activity, prepulse inhibition, and other behaviors.	[195, 196]
CHRNB4	Decreased anxiety (EPM); dose-dependent tolerance development; reduced somatic symptoms and hyperalgesia in nicotine withdrawal; delayed onset of nicotine withdrawal-induced behaviors; decreased somatic signs of nicotine withdrawal-induced symptoms; highly resistant to nicotine-induced seizures.	[109, 172, 181-186, 213, 216, 253]