Mice Lacking the beta 4 Subunit of the Nicotinic Acetylcholine Receptor Show Memory Deficits, Altered Anxiety- and Depression-Like Behavior, and Diminished Nicotine-Induced Analgesia

摘要

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.