Mice lacking the β4 subunit of the nicotinic acetylcholine receptor show memory deficits, altered anxiety- and depression-like behavior, and diminished nicotine-induced analgesia.

RATIONALE: The role of β4-containing nicotinic acetylcholine receptors (nAChRs) in cognition, anxiety, depression, and analgesia in the absence of nicotine is unclear.
METHODS: Wild-type (β4(+/+)) and knockout (β4(-/-)) mice for the nAChR β4 subunit were tested in behavioral tests assessing cognitive function, affective behaviors, and nociception.
RESULTS: There were no learning and memory deficits in β4(-/-) mice compared with β4(+/+) mice during the acquisition of the Barnes maze, contextual fear conditioning, and Y maze tasks. In the Barnes maze memory retention test, male β4(-/-) mice showed reduced use of the spatial search strategy, indicating small spatial memory deficits compared with β4(+/+) mice. In the cue-induced fear conditioning memory retention test, β4(-/-) mice exhibited reduced freezing time compared with β4(+/+) mice. Compared with β4(+/+) mice, β4(-/-) mice exhibited decreased anxiety-like behavior in the light-dark box. Depression-like behavior in β4(-/-) mice was decreased in the tail suspension test and increased in the forced swim test compared with β4(+/+) mice. β4(-/-) mice did not differ from β4(+/+) mice in basal nociception but were less sensitive to the antinociceptive effect of nicotine in 2 tests of acute thermal pain.
CONCLUSIONS: Lack of β4-containing nAChRs resulted in small deficits in hippocampus- and amygdala-dependent memory retention functions. β4-containing nAChRs are involved in anxiety- and depression-like behaviors and contribute to the analgesic effects of nicotine.