5-HT1c receptor is a prominent serotonin receptor subtype in the central nervous system.

Abstract

Neurons in rat central nervous system (CNS) that express 5-HT1c receptor mRNA have been localized by in situ hybridization histochemistry. The 5-HT1c receptor is expressed in a wide variety of cortical and subcortical neurons including hippocampal pyramidal neurons, neurons within most of the central monoaminergic cell groups, neurons in thalamic sensory relay nuclei, and neurons involved in the central processing and regulation of nociceptive transmission.Therefore, the 5-HTic receptor is a prominent but poorly characterized central subclass of serotonin (5-HT) receptor. The distribution of the 5-HTlc receptor within the CNS is considerably more widespread than that of the structurally and functionally related 5-HT2 receptor.The monoamine serotonin (5-hydroxytryptamine; 5-HT) functions as a neurotransmitter in the mammalian central and peripheral nervous systems (1). Within the brain, serotonergic neurons originate primarily in the raphe nuclei of the brainstem (2). The axons of these neurons project to most areas of the central nervous system (CNS) (3, 4), where they regulate a wide variety of sensory, motor, and cortical functions (5). The diverse actions of 5-HT are mediated by interactions with several distinct subclasses of 5-HT receptors. These multiple 5-HT receptors have been defined on the basis of their ligand-binding profile and include . Moreover, individual 5-HT receptor subtypes interact with distinct guanine nucleotide binding proteins and trigger different second-messenger pathways. Activation of the 5-HTla receptor results in an inhibition of adenylate cyclase, whereas activation of the 5-HT1c and 5-HT2 receptors activates phosphotidylinositol-specific phospholipase C, causing the release of the second messengers 1P3 and diacyl glycerol (9, 10).The diverse physiologic actions of 5-HT may not only derive from the activation of different intracellular signaling pathways but also from the expression of the individual receptor subtypes in distinct regions of the brain. Selective pharmacologic ligands have been used to determine the regional distribution of 5-HT receptors in the mammalian CNS. 5-HTla receptors are widely expressed in cortical and subcortical areas, whereas 5-HT2 receptors are detected at highest levels in the cerebral cortex (11, 12). The 5-HT1c subtype was first detected in choroid plexus epithelial cells (13)(14)(15) and is the only 5-HT receptor subtype expressed by these cells. However, the distribution of 5-HT1c receptors in other regions of the nervous system has been difficult because there are no selective ligands for this receptor subclass; most ligands that bind to 5-HT1c receptor also interact with 5-HT2 receptors.Recently, cDNA clones encoding the 5-HTla, 5-HT1c, and 5-HT2 receptors have been isolated and sequenced (16-18). The deduced amino acid sequences reveal that the 5-HT receptors share sequence and structural similarities with the family of guanine nucleotide-binding protein-coupled receptors thought to traverse the membrane seven times (19). The 5-HT1c an...

Central Serotonin2C Receptor: From Physiology to Pathology

“…High density is also found in the SNr, globus pallidus and ventro medial thalamus with low amounts detected in many other brain areas [110][111][112]. A widespread distribution of 5-HT 2C receptor mRNA has been demonstrated in rat, monkey and human brains using in situ hybridization techniques [113][114][115][116]. 5-HT 2C receptors are more abundant and more widely expressed in the brain than 5-HT 2A receptors, although there are several areas where both receptors coexist [117].…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…In-situ hybridization studies have demonstrated that 5-HT2C receptor mRNA is expressed in the VTA (Hoffman and Mezey, 1989;Molineaux et al, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997), both the pars compacta and pars reticulata subdivisions of the SN (Molineaux et al, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997), and in the terminal regions of the nigrostriatal and mesolimbic dopaminergic pathways: the striatum and the NA (Hoffman and Mezey, 1989;Pompeiano et al, 1994;Wright et al, 1995;Eberle-Wang et al, 1997). There is comparatively less evidence for 5-HT2C receptor mRNA in the PFC, however, several studies have shown the presence of 5-HT2C receptor mRNA in the cingulate or anterior cingulate cortex (Hoffman and Mezey, 1989;Pompeiano et al, 1994;Wright et al, 1995).…”

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

“…5-HT2C-Rs are highly expressed in the mPFC and amygdala (Abramowski et al, 1995;Clemett et al, 2000;Li et al, 2003;Lopez-Gimenez et al, 2002;Molineaux et al, 1989;Pompeiano et al, 1994;Sharma et al, 1997;Wright et al, 1995). Pharmacological studies point to a role for this receptor subtype in mediating serotonin's pro-anxiety effects at the level of the amygdala.…”