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ORIGINAL RESEARCH ARTICLE

13-cis-Retinoic Acid Alters Intracellular Serotonin, Increases 5-HT_1A Receptor, and Serotonin Reuptake Transporter Levels In Vitro

Kally C. O’Reilly^*, Simon Trent, Sarah J. Bailey^,1 and Michelle A. Lane^,1,2

^* Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712; Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY UK; and Department of Human Ecology, Division of Nutritional Sciences, The University of Texas at Austin, Austin, Texas 78712

To whom requests for reprints should be addressed at ² Department of Human Ecology, Division of Nutritional Sciences, Gearing Hall Room 115, Mail Stop A2700, The University of Texas at Austin, Austin, TX 78712. E-mail: mlane{at}mail.utexas.edu

In addition to their established role in nervous system development, vitamin A and related retinoids are emerging as regulators of adult brain function. Accutane (13-cis-retinoic acid, isotretinoin) treatment has been reported to increase depression in humans. Recently, we showed that chronic administration of 13-cis-retinoic acid (13-cis-RA) to adolescent male mice increased depression-related behaviors. Here, we have examined whether 13-cis-RA regulates components involved in serotonergic neurotransmission in vitro. We used the RN46A-B14 cell line, derived from rat embryonic raphe nuclei. This cell line synthesizes serotonin (5-hydroxytryptamine, 5-HT) and expresses the 5-HT_1A receptor and the serotonin reuptake transporter (SERT). Cells were treated with 0, 2.5, or 10 µM 13-cis-RA for 48 or 96 hrs, and the levels of 5-HT; its metabolite, 5-hydroxyindoleacetic acid (5HIAA); 5-HT_1A receptor; and SERT were determined. Treatment with 13-cis-RA for 96 hrs increased the intracellular levels of 5-HT and tended to increase intra-cellular 5HIAA levels. Furthermore, 48 hrs of treatment with 2.5 and 10 µM 13-cis-RA significantly increased 5-HT_1A protein to 168.5 ± 20.0% and 148.7 ± 2.2% of control respectively. SERT protein levels were significantly increased to 142.5 ± 11.1% and 119.2 ± 3.6% of control by 48 hrs of treatment with 2.5 and 10 µM of 13-cis-RA respectively. Increases in both 5-HT_1A receptor and SERT proteins may lead to decreased serotonin availability at synapses. Such an effect of 13-cis-RA could contribute to the increased depression-related behaviors we have shown in mice.

Key Words: 13-cis-retinoic acid • depression • serotonin • 5-HT_1A receptor • SERT

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				K. O'Reilly, S. J. Bailey, and M. A. Lane Retinoid-Mediated Regulation of Mood: Possible Cellular Mechanisms Experimental Biology and Medicine, March 1, 2008; 233(3): 251 - 258. [Abstract] [Full Text] [PDF]