Aghajanian G. K.

Albert P. R.

Anisman H.

Beste C.

Carlsson A.

Celada P.

Hesselgrave N.

Paul R. Albert


            The serotonin-1A (5-HT
            1A
            ) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre- and post-synaptic 5-HT
            1A
            receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre- versus post-synaptic 5-HT
            1A
            receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT
            1A
            receptor gene (
            Htr1a
            ). A functional polymorphism, rs6295 in the
            Htr1a
            promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT
            1A
            autoreceptor expression in animal models and humans. Its association with altered 5-HT
            1A
            expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene × environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT
            1A
            heteroreceptors, and rs6295-induced upregulation of 5-HT
            1A
            autoreceptors. Targeted therapeutics to inhibit 5-HT
            1A
            autoreceptor expression and induce 5-HT
            1A
            heteroreceptor expression may ameliorate treatment of anxiety and major depression.
          </jats:p

Crossref

Philosophical Transactions of the Royal Society B Biological Sciences

Transcriptional regulation of the 5-HT
            <sub>1A</sub>
            receptor: implications for mental illness

Transcriptional regulation of the 5-HT
                    1A

Transcriptional regulation of the 5-HT 1A

Abstract

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