13-cis-Retinoic acid alters intracellular serotonin, increases 5-HT1A receptor, and serotonin reuptake transporter levels in vitro.
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 microM 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 microM 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 microM 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.
O'Reilly
Kally C
KC
Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
Trent
Simon
S
Bailey
Sarah J
SJ
Lane
Michelle A
MA
D000818:Animals; D003879:Dermatologic Agents / Q000494:pharmacology*; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*
D003879:Dermatologic Agents; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D015474:Isotretinoin