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Altered anxiety-related responses in mutant mice lacking the beta4 subunit of the nicotinic receptor.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2003 Jul 16; Vol. 23 (15), pp. 6255-63. - Publication Year :
- 2003
-
Abstract
- Nicotine, acting at nicotinic acetylcholine receptors (nAChRs), is the primary addictive component of tobacco. Smokers often report an anxiolytic effect of cigarettes. This relief of anxiety, attributed to nicotine, is an important contributor to relapse when smokers try to quit. Hence, the study of the anxiolytic effects of nicotine is important for understanding the mechanisms underlying nicotine addiction. Mammalian nAChRs are pentameric ion channels usually composed of alpha andbeta subunits. Taking advantage of beta4-homozygous-null mice (beta4-/-), we examined the role of the nAChR beta4 subunit in anxiety-related behaviors. The beta4-/- mice behaved as though they were less anxious than wild-type littermates on the elevated-plus and staircase mazes, tests that measure anxiety-related behaviors. To obtain an independent, physiological indication of the stress produced by several tests, we measured changes in heart rate using telemetry. Consistently with the behavioral phenotype, beta4-/- mice had a smaller heart rate increase in the elevated-plus maze than did wild-type littermates. In contrast, during social isolation, a separate test for anxiety,beta4-/- mice exhibited a greater increase in heart rate than did wild-type littermates. Finally, beta4-/- mice were indistinguishable from their wild-type littermates in the open field, the light/dark box, and the mirrored chamber. The overall results demonstrate that beta4-containing (beta4*) nAChRs influence behavioral responses during anxiety-related tests, and that this effect depends on the type of anxiety-provoking experience. Through their influence on anxiety-related behavior, beta4* nAChRs might influence both tobacco consumption and smoking relapse.
- Subjects :
- Animals
Anxiety physiopathology
Behavior, Animal physiology
Brain metabolism
Densitometry
Electrocardiography, Ambulatory instrumentation
Female
Heart Rate genetics
Heart Rate physiology
Male
Maze Learning
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Protein Subunits biosynthesis
Protein Subunits deficiency
Protein Subunits genetics
RNA, Messenger biosynthesis
Receptors, Nicotinic biosynthesis
Receptors, Nicotinic deficiency
Social Isolation
Spatial Behavior
Stress, Physiological genetics
Stress, Physiological physiopathology
Telemetry
Tobacco Use Disorder etiology
Anxiety genetics
Receptors, Nicotinic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 23
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 12867510