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

Abstract

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. © The Author 2012. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.