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Age‐related changes in anxiety‐like behavior modified by expression of α4 subunit containing nicotinic acetylcholine receptors
Author(s) -
Anderson Shawn,
Brunzell Darlene
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1100.5
Subject(s) - anxiety , nicotinic acetylcholine receptor , protein subunit , endocrinology , population , elevated plus maze , receptor , medicine , nicotinic agonist , acetylcholine receptor , antagonist , psychology , acetylcholine , basal (medicine) , chemistry , pharmacology , psychiatry , biochemistry , environmental health , insulin , gene
Anxiety disorders are reduced in the geriatric population. Prior studies show that nicotinic acetylcholine receptors containing the α4 subunit (α4*nAChR; *other subunits co‐assemble to form a receptor) decline with age and are expressed in brain regions that regulate anxiety‐like behavior. This study evaluated 6, 12 and 24 month old (mo) wild type (WT) and heterozygous (α4HET; 1/2 WT α4*nAChR expression) male mice in a light‐dark box assay. Anxiety‐like behavior was reduced in 24 mo WT mice; they had reduced latencies to enter the light chamber and spent more time there compared to 6 mo WTs. Injection of a selective α4*nAChR antagonist (DHβE) and comparison to α4HET mice resulted in similar trends. Conversely, 24 mo α4HETs showed an increase in these anxiety‐like behaviors compared to 6 mo α4HET mice and injection of DHβE resulted in elevated latencies. Genotype‐and drug‐associated changes in exploratory behavior were not due to altered locomotor activity. Together with previous studies, these data suggest that reduced expression of α4*nAChRs may contribute to age‐related decreases in anxiety, but further suggest that inhibition of α4*nAChRs when basal levels are already decreased could elevate anxiety phenotype. These studies were supported by a Jeffress Memorial Trust research grant J‐951 and NIH R01 grant DA031289 to D.H. Brunzell. Training support for S.M. Anderson was provided by T32 DA00702736 to W.L. Dewey.