Central 5-HT receptors and their function; present and future

Abstract

Link to publication on Research at Birmingham portal General rightsUnless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law.• Users may freely distribute the URL that is used to identify this publication.• Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research.• User may use extracts from the document in line with the concept of 'fair dealing' under the Copyright, Designs and Patents Act 1988 (?) • Users may not further distribute the material nor use it for the purposes of commercial gain.Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.When citing, please reference the published version. Take down policyWhile the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.

GPCR signaling: role in mediating the effects of early adversity in psychiatric disorders

“…The perinatal window is also a period in which monoaminergic receptor composition, density, and functional coupling undergo major dynamic changes in the rodent brain prior to the establishment of adult‐like expression levels and function attained usually by the third to the sixth postnatal week [55]. Serotonin (5‐HT), dopamine (DA), and norepinephrine (NE), the three major monoaminergic neurotransmitters, contribute substantially in distinct perinatal temporal windows to the shaping of circuits that modulate emotionality, thus providing a neural substrate through which environmental perturbations such as early trauma can disrupt the programming of mood‐related behaviors [56–58]. Although our review is focussed predominantly on monoaminergic receptors, in particular 5‐HT receptors, it is of importance to note that other G protein signaling‐coupled neurotransmitter and neuropeptide receptors, including the metabotropic glutamate receptors (mGluRs) [38,59,60], GABA‐B receptors [61], muscarinic acetylcholine receptors [62], cannabinoid receptors (CB) [21,63], and the corticotropin‐releasing factor (CRF) receptors [47,64,65], have also been implicated in contributing to the effects of early stress on establishing perturbed emotionality (Fig.…”

Modulation of the Serotonergic Receptosome in the Treatment of Anxiety and Depression: A Narrative Review of the Experimental Evidence

“…5-HT 1A receptors are distributed in the limbic, cortical, and dorsal and median raphe nucleus (DRN and MRN), and are expressed in the pre- and post-synaptic membrane of neurons, where they act by regulating the extracellular serotonin concentration (5-HT) and transmission of the action potential. As an autoreceptor, it promotes the activation of internal rectifying potassium channels (GIRK), which allow an increase in potassium conductance, leading to neuron hyperpolarization, which in turn inhibits the opening of voltage-dependent calcium channels and the release of 5-HT [ 2 , 4 ]. In the post-synaptic membrane of non-serotonergic neurons, 5-HT 1A heteroreceptors, when stimulated by an agonist, activate the signal transduction pathway mediated by the Gα i/0 protein, which decreases cAMP synthesis and the activation of protein kinase A (PKA), which is responsible for the phosphorylation of proteins and enzymes downstream, such as the cAMP-responsive binding protein (CREB), an intranuclear transcription factor ( Figure 1 a).…”

“…As autoreceptors, when activated, they inhibit the release of 5-HT from the pre-synaptic terminal through the same mechanism observed for the other 5-HT 1A and 5-HT 1B serotonergic autoreceptors, changing potassium conductance and calcium influx. Although the mechanisms resulting from the activation of post-synaptic 5-HT 1D receptors have not yet been elucidated, it is known that they act through the inhibition of AC, common among 5-HT 1 receptors and that it is structurally similar to the 5-HT 1B receptor [ 2 , 17 , 18 ]. Likewise, the pharmacological mechanism of action of 5-ht 1e and 5-HT 1F serotonergic receptors is still unknown.…”

“…This diversity of receptors is comparable to that of more complex neurotransmitter systems, including glutamate and purines. Despite this, a wide range of agonists, antagonists, and selective radioligands are available for each subtype of 5-HT receptors, which has allowed further investigation of their location, signaling properties and functions in the CNS and in the rest of the organism [ 2 ].…”

The Association Between the Serotonin Receptor Type 1B (HTR1B) Gene rs13212041 Polymorphism and Trait Anxiety in China Han College Subjects

“…Discussion 5-HT1B receptor is a presynaptic and postsynaptic receptor widely distributed in the basal ganglia, hippocampus, and cortex. It plays important roles in multiple behavioral traits, such as locomotion, feeding, and thermoregulation, and also in arterial contractile regulation mechanisms and has been the focus of much neuropsychiatric and neuropharmacological research [38]. The intronless human HTR1B gene, which is located at 6q14.3-q16.3(GDB 132312), encodes a 390-amino-acid polypeptide.…”