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.

• Authors: Svetlana Semenova, Candice Contet, Amanda J Roberts, Athina Markou
• Journal: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (Nicotine Tob Res) Vol. 14 Issue 11 Pg. 1346-55 (Nov 2012) ISSN: 1469-994X [Electronic] England
• PMID: 22573727 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Analgesics
• Chrnb4 protein, mouse
• Nerve Tissue Proteins
• Receptors, Nicotinic
• Nicotine

Topics

• Amygdala (physiology)
• Analgesics (pharmacology)
• Animals
• Anxiety
• Behavior, Animal
• Cognition (physiology)
• Conditioning, Psychological
• Cues
• Depression (genetics)
• Fear
• Female
• Learning (physiology)
• Male
• Maze Learning
• Memory Disorders (genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity
• Nerve Tissue Proteins (genetics, metabolism)
• Nicotine (pharmacology)
• Receptors, Nicotinic (genetics, metabolism)