13-cis-retinoic acid alters intracellular serotonin, increases 5-HT1A receptor, and serotonin Reuptake transporter levels In Vitro

School of Human Ecology, University of Texas at Austin, Austin, Texas, United States
Experimental Biology and Medicine (Impact Factor: 2.23). 11/2007; 232(9):1195-203. DOI: 10.3181/0703-RM-83
Source: PubMed

ABSTRACT 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.

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Available from: Sarah J Bailey, Mar 20, 2014
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    • "The firing rate of serotoninergic neurons from the DRN can be regulated by 5-HT 1A autoreceptors, where a decrease in receptor number leads to increased basal firing activity (Richer et al., 2002) and 5- HT 1A receptor stimulation by 5-HT 1A agonists or increased intra-cellular 5-HT conversely decreases the firing activity of these neurons (Blier et al., 1998).13-Cis-RA, at 2.5 and 10 M, increased 5-HT 1A receptor and 5-HTT protein levels and intracellular 5-HT in vitro (O'Reilly et al., 2007). If these changes are recapitulated following 13-cis-RA treatment in vivo one would expect the activity of serotoninergic projections from the DRN to be diminished, potentially leading to an increase in depression-related behaviour. "
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