Abstract
Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems), which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.
Highlights
Serotonin is a monoamine neurotransmitter that plays an important role in physiological functions, such as sleep, feeding, sexual behavior, temperature regulation, pain, and cognition, as well as in pathological states including mood disorders, anxiety disorders, psychosis, and pain disorders.Medications that increase the level of 5-HT, such as the selective serotonin reuptake inhibitors, are used as treatments of depression and anxiety
Another major pathway of the 5-HT1A receptor is by activation of extracellular signal-regulated protein kinase (ERK), which has been implicated in various aspects of cell proliferation and differentiation [47]. 5-HT1A receptors were first reported to activate ERK by phosphorylation in non-neuronal cells expressing 5-HT1A receptors [48,49]
Activation of 5-HT1A receptor in Chinese hamster ovary (CHO) cells resulted in phosphatidylinositol-3 kinase (PI3K) dependent increased phosphorylation of ERK1/2 and Akt [22]. 5-HT dose-dependently induced activation of
Summary
Serotonin is a monoamine neurotransmitter that plays an important role in physiological functions, such as sleep, feeding, sexual behavior, temperature regulation, pain, and cognition, as well as in pathological states including mood disorders, anxiety disorders, psychosis, and pain disorders. 5-HT1A receptors are prFesent in high densities in limbic brain areas (hippocampus, lateral septum), cortical areas ( prefronthal and enthorinal cortex), as well as in the raphe nuclei, both dorsal and median [7] They are being found in the soma, in dendrite, in some cases in the hillock of neurons, and in the cell body and processes of astrocytes [8]. Local release of 5-HT in the raphe nuclei from axonal collaterals or crosstalk between different 5-HT neurons may diminish neuronal firing and produce a negative feedback regulation of transmitter release and may add an extra level of topographical specification Consistent with their role in regulating serotonergic tone, activation of autoreceptors limits the initial increase of the extracellular 5-HT levels induced by selective serotonin reuptake inhibitors (SSRIs), and delay their therapeutic response [11,12]. It was shown that the activation of 5-HT1B heteroceptors induces antidepressant-like effect in mice [20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
