Semenova_2012_Nicotine.Tob.Res_14_1346

RATIONALE: The role of beta4-containing nicotinic acetylcholine receptors (nAChRs) in cognition, anxiety, depression, and analgesia in the absence of nicotine is unclear.
METHODS: Wild-type (beta4(+/+)) and knockout (beta4(-/-)) mice for the nAChR beta4 subunit were tested in behavioral tests assessing cognitive function, affective behaviors, and nociception.
RESULTS: There were no learning and memory deficits in beta4(-/-) mice compared with beta4(+/+) mice during the acquisition of the Barnes maze, contextual fear conditioning, and Y maze tasks. In the Barnes maze memory retention test, male beta4(-/-) mice showed reduced use of the spatial search strategy, indicating small spatial memory deficits compared with beta4(+/+) mice. In the cue-induced fear conditioning memory retention test, beta4(-/-) mice exhibited reduced freezing time compared with beta4(+/+) mice. Compared with beta4(+/+) mice, beta4(-/-) mice exhibited decreased anxiety-like behavior in the light-dark box. Depression-like behavior in beta4(-/-) mice was decreased in the tail suspension test and increased in the forced swim test compared with beta4(+/+) mice. beta4(-/-) mice did not differ from beta4(+/+) mice in basal nociception but were less sensitive to the antinociceptive effect of nicotine in 2 tests of acute thermal pain.
CONCLUSIONS: Lack of beta4-containing nAChRs resulted in small deficits in hippocampus- and amygdala-dependent memory retention functions. beta4-containing nAChRs are involved in anxiety- and depression-like behaviors and contribute to the analgesic effects of nicotine.