The serotonin has been known to play important roles in pathology of the mood disorders. We summerize the evidences of serotonin in pathology of the mood disorders in a view of neuroanatomical and neurochemical aspects. Nowaday, the selective serotonin reuptake inhibitors(SSRIs)may be practically the first line of antidepressants with traditional tricyclic antidepressants(TCAs. Authors review the role of serotonin in the treatment of the mood disorders, in a view of the general considerations in selecting antidepressants, pharmacology, therapeutic, indications, side effects, doses of medication, drug-discontinuation syndrome, drug-to-drug interactions, and special therapeutic situations.
Antidepressive Agents ; Mood Disorders* ; Pathology* ; Pharmacology ; Serotonin*

5-hydroxtryptamine (5-HT, serotonin) has been recognized not only as a neurotransmitter and vasoactive agent, but also as a growth factor. 5-HT mainly binds to 5-HT(2) receptors or 5-HT(1) receptors on cell surface to stimulate cell proliferation through Ras or MAPK pathway in many cell types. It has been reported that 5-HT stimulates megakaryocytopoiesis via 5-HT receptors. The possible mechanism of 5-HT on the proliferation and differentiation of megakaryocytes (MK) has been discussed in this review article. In early stage of megakaryocytopoiesis, 5-HT may bind to 5-HT(2B) receptor on megakaryocytes, and promotes their proliferation and differentiation. In the late stage, 5-HT may involve in the platelet release procedure by inducing nitric oxide (NO) synthesis via 5-HT(2A) receptors. 5-HT can also antagonize the apoptotic effect induced by thrombospondin-1 (TSP-1) which is a platelet alpha granule protein and has synergic effect with platelet-derived growth factor (PDGF) to enhance megakaryocytes proliferation. Therefore, 5-HT is likely to be an important substance in the feedback regulation of thrombopoiesis. In this review the 5-HT and its receptors, 5-HT as cell growth factor, pathway of 5-HT stimulating cell proliferation and influance of 5-HT on MK-progenitor cells were summarized.
Humans ; Megakaryocytes ; physiology ; Receptors, Serotonin ; metabolism ; Receptors, Serotonin, 5-HT2 ; metabolism ; Serotonin ; metabolism ; pharmacology ; Thrombopoiesis ; physiology ; Thrombopoietin ; physiology

We tried to review and update clinical and preclinical studies evaluating vilazodone's role as an antidepressant for patients with major depressive disorder (MDD). In terms of its mechanism of actions, we sought to elaborate them mainly through preclinical animal studies. A data search was conducted in November 1, 2013, using the key terms "vilazodone" or "Viibryd," in PubMed and Medline databases. All published and unpublished studies are included and citations from publications were also reviewed for additional references. Five unpublished, phase-II and two pivotal published phase-III clinical trials with nearly identical design (8-week, double-blind, randomized, and placebo-controlled) investigated efficacy of vilazodone, were found for the treatment of patients with MDD. Two post-hoc studies and one long-term open study were also included. Data were thoroughly reviewed to incorporate the pharmacology, action mechanism, efficacy and safety for the vilazodone in the treatment of major depressive disorder. Vilazodone is an antidepressant with novel mechanism of action because its chemical structure is unrelated to conventional antidepressant, and it has a selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist profile. Vilazodone is an effective and safe treatment option with its novel action mechanisms for patients with depression. Its putative benefits compared with other antidepressants must be thoroughly studied in adequately-powered and well-designed future clinical trials.
Animals ; Antidepressive Agents ; Depression ; Depressive Disorder, Major* ; Humans ; Pharmacology ; Receptor, Serotonin, 5-HT1A ; Serotonin ; Vilazodone Hydrochloride

Heidenhain pouch secretion in response to small dose of serotonin was studied in conscious dogs. A single subcutaneous injection of 0.5 to 2.0 mg of serotonin produced no changes in spontaneous fasting secretion; however, the milk-induced secretion was greatly inhibited by the same dose. This inhibition was abolished by treatment of dibenzyline or LSD(d-lysergic acid die- thylamide). LSD alone enhanced the response of gastric secretion to milk. Constant intravenous infusion of serotonin, at levels of 3 to 10 microgram/kg/min was associated with a significant increase in the volume of gastric juice aspirated from three anesthetized dogs, but the acidity of juice varied very slightly. However, when histamine is given as much as 0.8 to 3 microgram/kg/min, a marked increase in both the volume and acidity was observed. A significant elevation of mucin content in the juice obtained from the Heidenhain pouch was seen in dogs receiving a single subcutaneous injection of 1.0 mg of serotonin. In case of histamine, the mucin content of pouch juice was not relatively increased and merely an increase in the total amount of mucin secondary to the volume increase was seen. The observed increase in mucin by serotonin was inhibited by LSD, BOL (2-bromo-d-lysergic acid diethylamide) or dibenzyline, and mildly by morphine. Atropine or hexamethonium did not block the response of mucin production to serotonin. The gastrointestinal motility elicited by serotonin was not affected by these agents. It is felt that the receptor(s) responsible for the mucin production in the dog belongs to the D-receptor types postulated by Gaddum and Picarelli.
Animals ; Dogs ; Gastric Juice/*drug effects ; Secretory Rate ; Serotonin/*pharmacology

1. 5-HT inhibits spontaneous fluid secretion as well as stimulated secretion with secretin (cAMP mediated) or ACh (Ca2+ mediated) in the isolated guinea pig pancreatic ducts. 2. The inhibitory effect of 5-HT is reversible and is dependent on the concentration in the range 0.01-0.1 microM, which is much lower than those that affect intestinal motility and secretion. 3. The 5-HT3 receptor in duct cells appears to mediate the inhibitory effect of 5-HT. 4. [Ca2+]i is unlikely to mediate the inhibitory effect of 5-HT.
5-Methoxytryptamine/pharmacology ; Acetylcholine/pharmacology ; Animal ; Calcium/metabolism ; Guinea Pigs ; Pancreatic Ducts/metabolism* ; Pancreatic Ducts/drug effects ; Secretin/pharmacology ; Serotonin/pharmacology ; Serotonin/metabolism* ; Serotonin/analogs & derivatives* ; Vasodilator Agents/pharmacology

OBJECTIVETo investigate the effects of serotonin (5-HTIA) receptors in the hippocampal dentate gyrus (DG) on active avoidance learning in rats.

METHODSTotally 36 SD rats were randomly divided into control group, antagonist group and agonist group(n = 12). Active avoidance learning ability of rats was assessed by the shuttle box. The extracellular concentrations of 5-HT in the DG during active avoidance conditioned reflex were measured by microdialysis and high performance liquid chromatography (HPLC) techniques. Then the antagonist (WAY-100635) or agonist (8-OH-DPAT) of the 5-HT1A receptors were microinjected into the DG region, and the active avoidance learning was measured.

RESULTS(1) During the active avoidance learning, the concentration of 5-HT in the hippocampal DG was significantly increased in the extinction but not establishment in the conditioned reflex, which reached 164.90% ± 26.07% (P <0.05) of basal level. (2) The microinjection of WAY-100635 (an antagonist of 5-HT1A receptor) into the DG did not significantly affect the active avoidance learning. (3) The microinjection of 8-OH-DPAT(an agonist of 5-HT1A receptor) into the DG significantly facilitated the establishment process and inhibited the extinction process during active avoidance conditioned reflex.

CONCLUSIONThe data suggest that activation of 5-HT1A receptors in hipocampal DG may facilitate active avoidance learning and memory in rats.

8-Hydroxy-2-(di-n-propylamino)tetralin ; pharmacology ; Animals ; Avoidance Learning ; Dentate Gyrus ; physiology ; Piperazines ; pharmacology ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT1A ; physiology ; Serotonin ; physiology ; Serotonin Receptor Agonists ; pharmacology

A series of biarylbenzamidine analogs were synthesized and tested for their biological activities of inhibiting the reuptake of 5-HT. All of them were new compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibition activity. Among the tested compounds, 5i, 4a and 5m exhibited potent inhibitory activity against 5-HT reuptake in vitro. It is a chance to find a better precursor of SSRIs (selective serotonin reuptake inhibitors) for further optimization of compounds.
Animals ; Antidepressive Agents ; chemical synthesis ; pharmacology ; Benzamidines ; chemical synthesis ; pharmacology ; Male ; Mice ; Rats ; Rats, Wistar ; Serotonin ; analysis ; Serotonin Uptake Inhibitors ; chemical synthesis ; pharmacology ; Structure-Activity Relationship

Anxiety disorders are a common mental illness that seriously endangered physical and mental health of human beings. The etiology of anxiety disorders is closely related to the abnormality of monoamines neurotransmitters, amino acids neurotransmitters and neuropeptides. The long-term use of anti-anxiety chemical drugs has some adverse effects, such as constipation, muscle relaxation, lethargy, tolerance and withdrawal symptoms. However, traditional Chinese medicines have advantages of multi-component, multi-target coordination, with less adverse reactions. Therefore, it is a promising prospect to develop novel anti-anxiety drugs from traditional Chinese medicines and formulas. This article reviewed some traditional Chinese medicines and formulas that can relieve anxiety symptoms. These include traditional Chinese medicines(Panax ginseng, Lycium ruthenium, Morus alba, Bupleurum plus dragon bone oyster soup, Chailong Jieyu Pills, and Naogongtai Formulas) with the effect on monoamine neurotransmitters, such as serotonin, dopamine, and norepinephrine; traditional Chinese medicines(Rehmannia glutinosa, Ziziphus jujuba Mill. var. spinosa, Jielv Anshen Decoction, Baixiangdan Capsules, Antianxietic Compound Prescription Capsules) with the effect on amino acid neurotransmitters, such as glutamic acid, γ-aminobutyrc acid; and traditional Chinese medicines(P. ginseng, Xiaoyao San, Shuyu Ningxin Decoction)with the effect on neuropeptide Y pathway, with the aim to provide theoretical basis for the further development of some novel and more effective anti-anxiety therapeutics from traditional Chinese medicine and formulas.
Anti-Anxiety Agents/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Medicine, Chinese Traditional ; Neurotransmitter Agents ; Norepinephrine ; Serotonin

Serotonin receptor subtype 6 (5-HT(6)) is a neurotransmitter receptor, which is involved in various brain functions such as memory and mood. It mediates signaling via the interaction with a stimulatory G-protein. Especially, the third intracellular loop (iL3) of 5-HT(6) and the alpha subunit of stimulatory G protein (Galpha(s)) are responsible for the signaling process of 5-HT(6). Chemical compounds that could inhibit the interaction between the iL3 region of 5-HT(6) and Galpha(s) were screened from a chemical library consisted of 5,600 synthetic compounds. One of the identified compounds bound to Galpha(s) and effectively blocked the interaction between Galpha(s) and the iL3 region of 5-HT(6). The identified compound was further shown to reduce the serotonin-induced accumulation of cAMP in 293T cells transformed with 5-HT(6) cDNA. It also lowered the Ca2+ efflux induced by serotonin in cells expressing 5-HT(6) and chimeric Galpha(s5/q). These results indicate that the interaction between the iL3 of 5-HT(6) and Galpha(s) can be exploited for screening of regulatory compounds against the signaling pathway of 5-HT(6).
Animals ; Calcium/metabolism ; Cell Line ; Cephalosporins/*pharmacology ; Cricetinae ; Cricetulus ; Cyclic AMP/biosynthesis ; GTP-Binding Protein alpha Subunits, Gs/antagonists & inhibitors/*metabolism ; Humans ; Receptors, Serotonin/*drug effects/metabolism/*physiology ; Serotonin/pharmacology ; Serotonin Antagonists/pharmacology ; Signal Transduction

AIMTo determine whether serotonin, a major neurotransmitter in brain, can modulate the production of secretory beta-amyloid protein precursor (sAPP) by activation of serotonin 5-HT2C receptor.

METHODSThe hippocampal slices of rats were incubated with various concentrations of serotonin, M-110, or L-107. sAPP released into the incubation medium were assayed by Western blot analysis assay with monoclonal antibody 22C11 for 2 h.

RESULTSVarious concentrations of serotonin (1.0 x 10(-2) - 1.0 x 10(3) micromol x L(-1)), M-110, a serotonin 5-HT2C agonist (1.5 x 10(-6) - 1.5 x 10(3) micromol x L(-1)), showed positive effect on the production of sAPP while L-107, a serotonin 5-HT2C antagonist (1.0 x 10(-9) - 1.0 x 10(3) micromol x L(-1)), showed negative effect on the production of sAPP over controls.

CONCLUSIONSerotonin modulates production of secretory amyloid beta-protein precursor through serotonin 5-HT2C receptor in incubated rat hippocampal slices.

Amyloid beta-Protein Precursor ; secretion ; Animals ; Hippocampus ; metabolism ; In Vitro Techniques ; Male ; Peptide Fragments ; secretion ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2C ; Serotonin ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists