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Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.
- Source :
-
Genes, brain, and behavior [Genes Brain Behav] 2009 Jun; Vol. 8 (4), pp. 398-406. Date of Electronic Publication: 2009 Feb 11. - Publication Year :
- 2009
-
Abstract
- Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.
- Subjects :
- Animals
Cells, Cultured
Corticosterone blood
Corticotropin-Releasing Hormone metabolism
Depression genetics
Depression psychology
Diestrus
Female
Genotype
Hindlimb Suspension
Hypothalamo-Hypophyseal System drug effects
Hypothalamo-Hypophyseal System physiology
Hypothalamus metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity drug effects
Pituitary-Adrenal System drug effects
Pituitary-Adrenal System physiology
Reverse Transcriptase Polymerase Chain Reaction
Anxiety psychology
Behavior, Animal drug effects
Estrous Cycle drug effects
Progesterone pharmacology
Receptors, Nicotinic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1601-183X
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Genes, brain, and behavior
- Publication Type :
- Academic Journal
- Accession number :
- 19220484
- Full Text :
- https://doi.org/10.1111/j.1601-183X.2009.00476.x