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Lithium treatment attenuates muscarinic M1 receptor dysfunction
Article first published online: 15 JUN 2011
© 2011 John Wiley and Sons A/S
Volume 13, Issue 3, pages 238–249, May 2011
How to Cite
Creson, T. K., Austin, D. R., Shaltiel, G., McCammon, J., Wess, J., Manji, H. K. and Chen, G. (2011), Lithium treatment attenuates muscarinic M1 receptor dysfunction. Bipolar Disorders, 13: 238–249. doi: 10.1111/j.1399-5618.2011.00915.x
The authors of this paper report no biomedical financial interests or potential conflicts of interest in connection with this manuscript. HKM and GC are now at Johnson & Johnson Pharmaceutical Research and Development; all of this work was conducted while they were employees of the National Institute of Mental Health.
- Issue published online: 15 JUN 2011
- Article first published online: 15 JUN 2011
- Received 9 June 2010, revised and accepted for publication 23 January 2011
Figure S1. M1 expression following chronic valproate treatment. Expression of M1 protein in frontal cortical tissue was compared between control- and valproate-treated male Wistar Kyoto rats. No significant difference was detected.
Figure S2. Lithium levels in the brain and serum. Male wild-type (WT) and M1 knockout (KO) mice were chronically treated with control and lithium-treated chow, and lithium levels were determined as described in the Materials and Methods. Lithium concentrations were significantly elevated in the serum (A) and brain tissue (B) of both WT and KO mice, and no significant effects of genotype on lithium levels were detected [Serum: F(1,20)treatment = 141.7, p < 0.0001; F(1,20)genotype = 0.1453, p = 0.7071; Brain: F(1,20)treatment = 234.9, p < 0.0001; F(1,20)genotype = 0.03903, p = 0.6766].
Figure S3. Effects of M1 ablation and chronic lithium treatment on frontal cortical phospho-MARCKS level. Adult male M1 knockout (KO) and wild-type (WT) littermates were bred, housed, and treated with lithium-treated or control chow as described in the Materials and Methods. One week after the last behavioral experiment, frontal cortical tissues were obtained and assayed to detect levels of phospho-MARCKS (pMARCKS) and total MARCKS. Representative blots of pMARCKS and MARCKS are shown in (A) and pMARCKS expression is presented quantitatively in (B). No significant effects on pMARCKS were found [F(1,16)genotype = 0.1381, p = 0.7150; F(1,16)treatment = 0.1344, p = 0.7187].
Figure S4. Effects of M1 ablation and chronic lithium treatment on additional outcome measures of the elevated-plus-maze test. Adult male M1 knockout (KO) and wild-type (WT) littermates were bred, housed, and treated with lithium-treated or control chow as described in the Materials and Methods, and then tested in the elevated-plus-maze test. (A) A significant genotype effect was detected for time spent in the closed arms [two-way ANOVA, F(1,20)genotype = 4.461, p = 0.0475; F(1,20)treatment = 0.7377, p = 0.4006; F(1,20)interaction = 0.9536, p = 0.3405]. (B) No significant difference was detected for distance traveled in the closed arms (two-way ANOVA). Data are means ± SEMs. * indicates p < 0.05. Letter G in the graph indicates a comparison between genotype only.
Supplementary materials and methods: Determining plasma and brain lithium levels.
Table S1. M1 is a predicted target of the mood stabilizer-responsive miRNAs let-7b and let-7c.
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