PT  - JOURNAL ARTICLE
AU  - Vincent Martin
AU  - Lionel Mathieu
AU  - Jorge Diaz
AU  - Haysam Salman
AU  - Jeanine Alterio
AU  - Caroline Chevarin
AU  - Laurence Lanfumey
AU  - Michel Hamon
AU  - Mark C. Austin
AU  - Michèle Darmon
AU  - Craig A. Stockmeier
AU  - Justine Masson
TI  - Key role of the 5-HT1A receptor addressing protein Yif1B in serotonin neurotransmission and SSRI treatment
AID  - 10.1503/jpn.190134
DP  - 2020 Sep 01
TA  - Journal of Psychiatry and Neuroscience
PG  - 344--355
VI  - 45
IP  - 5
4099  - http://jpn.ca/content/45/5/344.short
4100  - http://jpn.ca/content/45/5/344.full
SO  - J Psychiatry Neurosci2020 Sep 01; 45
AB  - Background: Altered function of serotonin receptor 1A (5-HT1AR) has been consistently implicated in anxiety, major depressive disorder and resistance to antidepressants. Mechanisms by which the function of 5-HT1AR (expressed as an autoreceptor in serotonergic raphe neurons and as a heteroreceptor in serotonin [5-HT] projection areas) is altered include regulation of its expression, but 5-HT1AR trafficking may also be involved.Methods: We investigated the consequences of the lack of Yif1B (the 5-HT1AR trafficking protein) on 5-HT neurotransmission in mice, and whether Yif1B expression might be affected under conditions known to alter 5-HT neurotransmission, such as anxious or depressive states or following treatment with fluoxetine (a selective serotonin reuptake inhibitor) in humans, monkeys and mice.Results: Compared with wild-type mice, Yif1B-knockout mice showed a significant decrease in the forebrain density of 5-HT projection fibres and a hypofunctionality of 5-HT1A autoreceptors expressed on raphe 5-HT neurons. In addition, social interaction was less in Yif1B-knockout mice, which did not respond to the antidepressant-like effect of acute fluoxetine injection. In wild-type mice, social defeat was associated with downregulated Yif1B mRNA in the prefrontal cortex, and chronic fluoxetine treatment increased Yif1B expression. The expression of Yif1B was also downregulated in the postmortem prefrontal cortex of people with major depressive disorder and upregulated after chronic treatment with a selective serotonin reuptake inhibitor in monkeys.Limitations: We found sex differences in Yif1B expression in humans and monkeys, but not in mice under the tested conditions.Conclusion: These data support the concept that Yif1B plays a critical role in 5-HT1AR functioning and brain 5-HT homeostasis. The opposite changes in its expression observed in anxious or depressive states and after therapeutic fluoxetine treatment suggest that Yif1B might be involved in vulnerability to anxiety and depression, and fluoxetine efficacy.