The serotonergic mechanisms have been successfully utilized by the majority of antidepressant drug discovery programmes, while the search for newer targets remains persistent. The present review focused on the serotonin type-3 receptor, the only ion channel subtype in the serotonin family. Behavioural, neurochemical, electrophysiological and molecular analyses, including the results from our laboratory, provided substantial evidence that rationalizes the correlation between serotonin type-3 receptor modulation and rodent depressive-like behaviour. Nevertheless, the reports on polymorphism of serotonin type-3 receptor genes and data from clinical studies (on serotonin type-3 receptor antagonists) were insufficient to corroborate the involvement of this receptor in the neurobiology of depression. The preclinical and clinical studies that have contradicted the antidepressant-like effects of serotonin type-3 receptor antagonists and the reasons underlying such disagreement were discussed. Finally, this critical review commended the serotonin type-3 receptor as a candidate neuronal antidepressant drug target.
Adrien J., Tissier MH, Lanfumey L., et al. (1992) Central action of 5-HT3 receptor ligands in the regulation of sleepwakefulness and raphe neuronal activity in the rat . Neuropharmacology31: 519-529.
2.
Aina Y., Susman JL ( 2006) Understanding comorbidity with depression and anxiety disorders. J Am Osteopath Assoc106: S9-S14.
3.
Ait-Daoud N., Johnson BA, Prihoda TJ, Hargita ID ( 2001) Combining ondansetron and naltrexone reduces craving among biologically predisposed alcoholics: preliminary clinical evidence. Psychopharmacology154: 23-27.
4.
Alex KD, Pehek EA ( 2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Therapeut113: 296-320.
5.
Anttila SAK, Leinonen EVJ ( 2001) A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev7: 249-264.
6.
Arnold LM ( 2008) Management of fibromyalgia and comorbid psychiatric disorders . J Clin Psychiat69: 14-19.
7.
Bagdy E., Solyom S., Harsing LG, Jr ( 1998) Feedback stimulation of somatodendritic serotonin release: a 5-HT3 receptor-mediated effect in the raphe nuclei of the rat. Brain Res Bull45: 203-208.
Barnes NM, Hales TG, Lummis SC, Peters JA (2009) The 5-HT3 receptor-the relationship between structure and function. Neuropharmacology56: 273-284.
10.
Barnes NM, Sharp T. ( 1999) A review of central 5-HT receptors and their function . Neuropharmacology38: 1083-1152.
11.
Becker C., Zeau B., Rivat C., Blugeot A., Hamon M., Benoliel JJ ( 2008) Repeated social defeat-induced depression-like behavioural and biological alterations in rats: involvement of cholecystokinin . Mol Psychiatr13: 1079-1092.
12.
Belelli D., Balcarek JM, Hope AG, Peters JA, Lambert JJ, Blackburn TP ( 1995) Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. Mol Pharmacol48: 1054-1062.
Berendsen HHG ( 1995) Interactions between 5-hydroxytryptamine receptor subtypes: is a disturbed receptor balance contributing to the symptomatology of depression in humans? Pharmacol Ther66:17-37.
15.
Berendsen HHG, Broekkamp CL ( 1997) Indirect in vivo 5-HT1Aagonistic effects of the new antidepressant mirtazapine. Psychopharmacology133: 275-282.
16.
Berk M., Ichim C., Brook S. ( 2001) Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Int Clin Psychopharm16: 87-92.
17.
Bhatnagar S., Nowak N., Babich L., Bok L. ( 2004) Deletion of the 5-HT3 receptor differentially affects behaviour of males and females in the Porsolt forced swim and defensive withdrawal tests. Behav Brain Res153: 527-535.
18.
Blandina P., Goldfarb J., Craddock-Royal B., Green JP ( 1989) Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum. J Pharmacol Exp Ther251: 803-809.
19.
Blandina P., Goldfarb J., Walcott J., Green JP ( 1991) Serotonergic modulation of the release of endogenous norepinephrine from rat hypothalamic slices. J Pharmacol Exp Ther256: 341-347.
20.
Blier P., Bouchard C. ( 1993) Functional characterization of a 5-HT3 receptor which modulates the release of 5-HT in the guinea-pig brain. Brit J Pharmacol108: 13-22.
21.
Blier P., Monroe PJ, Bouchard C., Smith DL, Smith DJ ( 1993) 5-HT3 receptors which modulate [3H]5-HT release in the guinea-pig hypothalamus are not autoreceptors. Synapse15: 143-148.
22.
Bloom FE, Morales M. ( 1998) The central 5-HT3 receptor in CNS disorders. Neurochem Res23: 653-659.
23.
Boess FG, Beroukhim R., Martin IL ( 1995) Ultrastructure of the 5-hydroxytryptamine 3 receptor . J Neurochem64: 1401-1405. Boess FG, Martin IL ( 1994) Molecular biology of 5-HT receptors. Neuropharmacology33: 275-317.
24.
Borsini F. ( 1995) Role of the serotonergic system in the forced swimming test. Neurosci Biobehav R19: 377-395.
25.
Borsini F., Cesana R., Vidi A., Mennini T. ( 1991) Evidence that imipramine activates 5-HT1C receptor function . Eur J Pharmacol203: 359-363.
26.
Bourin M., Hascoet M., Colombel MC, Redrobe JP, Baker GB ( 1996) Differential effects of clonidine, lithium and quinine in the forced swimming test in mice for antidepressants: possible roles of serotoninergic systems. Eur Neuropsychopharm6: 231-236.
27.
Bourin M., Redrobe JP, Baker GB ( 1998) Pindolol does not act only on 5-HT1A receptors in augmenting antidepressant activity in the mouse forced swimming test. Psychopharmacology136: 226-234.
28.
Bradbury AJ, Costall B., Domeney AM, Naylor RJ ( 1985) Laterality of dopamine function and neuroleptic action in the amygdala in the rat. Neuropharmacology24: 1163-1170.
29.
Bradley PB, Engel G., Feniuk W., et al. (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology25: 563-576.
30.
Brady CA, Dover TJ, Massoura AN, Princivalle AP, Hope AG, Barnes NM ( 2007) Identification of 5-HT3A and 5-HT3B receptor subunits in human hippocampus. Neuropharmacology52: 1284-1290.
31.
Braun DL, Sunday SR, Halmi KA ( 1994) Psychiatric comorbidity in patients with eating disorders . Psychol Med24: 859-867.
32.
Bravo G., Maswood S. ( 2006) Acute treatment with 5-HT3 receptor antagonist, tropisetron, reduces immobility in intact female rats exposed to the forced swim test. Pharmacol Biochem Be85: 362-368.
33.
Brown AM, Hope AG, Lambert JJ, Peters JA ( 1998) Ion permeation and conduction in a human recombinant 5-HT3 receptor subunit (h5-HT3A). J Physiol507: 653-665.
34.
Brüss M., Barann M., Hayer-Zillgen M., Eucker T., Göthert M., Bönisch H. ( 2000) Modified 5-HT3A receptor function by co-expression of alternatively spliced human 5-HT3A receptor iso-forms. N-S Arch Pharmacol362: 392-401.
35.
Brüss M., Göthert M., Hayer M., Bönisch H. ( 1998) Molecular cloning of alternatively spliced human 5-HT3 receptor cDNAs. Ann NY Acad Sci861: 234-235.
36.
Bufton KE, Steward LJ, Barber PC, Barnes NM ( 1993) Distribution and characterization of the [3H] granisetron-labelled 5-HT3 receptor in the human forebrain. Neuropharmacology32: 1325-1331.
37.
Buskila D., Cohen H. ( 2007) Comorbidity of fibromyalgia and psychiatric disorders . Curr Pain Headache Rep11: 333-338.
38.
Cameron OG ( 2006) Anxious-depressive comorbidity: effects on HPA axis and CNS noradrenergic functions. Essent Psychopharmacol7: 24-34.
Chau DT, Rada P., Kosloff RA, Taylor JL, Hoebel BG ( 2001) Nucleus accumbens muscarinic receptors in the control of behavioural depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test. Neuroscience104: 791-798.
41.
Chen JP, van Praag HM, Gardner EL ( 1991) Activation of 5-HT3 receptor by 1-phenylbiguanide increases dopamine release in the rat nucleus accumbens. Brain Res543: 354-357.
42.
Choi JS, Choi BH, Ahn HS, et al. (2003) Mechanism of block by fluoxetine of 5-hydroxytryptamine3 (5-HT3)-mediated currents in NCB-20 neuroblastoma cells. Biochem Pharmacol66: 2125-2132.
43.
Costall B., Domeney AM, Gerrard PA, Kelly ME, Naylor RJ, Tyers MB ( 1987a) Effects of the 5-HT3 receptor antagonists GR38032F, ICS 215-930 and BRL 43694 in tests for anxiolytic activity. Brit J Pharmacol91: 195P.
44.
Costall B., Domeney AM, Naylor RJ, Tyers MB ( 1987b) Effects of the 5-HT3 receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain. Brit J Pharmacol92: 881-894.
45.
Costall B., Naylor NJ ( 2004) 5-HT3 Receptors. Curr Drug Targets. CNS and Neurological Disorders3: 27-37.
46.
Costall B., Naylor RJ, Tyers MB ( 1990) The psychopharmacology of 5-HT3 receptors. Pharmacol Therapeut47: 181-202.
47.
Crespi D., Gobbi M., Mennini T. ( 1997) 5-HT3 serotonin hetero-receptors inhibit [3H] acethylcholine release in rat cortical synaptosomes. Pharmacol Res35: 351-354.
48.
Cryan JF, Valentino RJ, Lucki I. ( 2005) Assessing substrates underlying the behavioural effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav R29: 547-569.
49.
Davies PA, Pistis M., Hanna MC, et al. (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature397: 359-363.
50.
Davis L., Uezato A., Newell JM, Frazier E. ( 2008) Major depression and comorbid substance use disorders . Curr Opin Psychiatr21: 14-18.
51.
Dawes MA, Johnson BA, Ait-Daoud N., Ma JZ, Cornelius JR ( 2005a) A prospective, open-label trial of ondansetron in adolescents with alcohol dependence. Addict Behav30: 1077-1085.
52.
Dawes MA, Johnson BA, Ma JZ, Ait-Daoud N., Thomas SE, Cornelius JR ( 2005b) Reductions in and relations between ‘‘craving’’ and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependence. Addict Behav30: 1630-1637.
53.
De Deurwaerdere P., Moison D., Navailles S., Porras G., Spampinato U. ( 2005) Regionally and functionally distinct serotonin-3 receptors control in vivo dopamine outflow in the rat nucleus accumbens. J Neurochem94: 140-149.
54.
Delgado PL, Moreno FA ( 2000) Role of norepinephrine in depression. J Clin Psychiat61: 5-12.
55.
Dépôt M., Caillé G., Mukherjee J., Katzman MA, Cadieux A., Bradwejn J. ( 1999) Acute and chronic role of 5-HT3 neuronal system on behavioural and neuroendocrine changes induced by intravenous cholecystokinin tetrapeptide administration in humans. Neuropsychopharmacology20: 177-187.
56.
De Vry J., Melon C., Jentzsch K.R., Schreiber R. ( 1997) Identification of 5-HT receptor subtypes responsible for the therapeutic effects of selective 5-HT reuptake inhibitors (SSRIs) . Biol Psychiatry42: 67S-68S.
Dolnak DR ( 2006) Treating patients for comorbid depression, anxiety disorders, and somatic illnesses. J Am Osteopath Assoc106: S1-S8.
59.
Dorostkar MM, Boehm S. ( 2007) Opposite effects of presynaptic 5-HT3 receptor activation on spontaneous and action potential-evoked GABA release at hippocampal synapses . J Neurochem100: 395-405.
60.
Doucet E., Miquel MC, Nosjean A., Verge ÂD, Hamon M., Emerit MB ( 2000) Immunolabeling of the rat central nervous system with antibodies partially selective of the short form of the 5-HT3 receptor . Neuroscience95: 881-892.
61.
Dremencov E., Weizmann Y., Kinor N., Gispan-Herman I., Yadid G. ( 2006) Modulation of dopamine transmission by 5HT2C and 5HT3 receptors: a role in the antidepressant response. Curr Drug Targets7: 165-175.
62.
Dubin AE, Huvar R., D’Andrea MR, et al. (1999) The pharmacological and functional characteristics of the serotonin 5-HT3A receptor are specifically modified by a 5-HT3B receptor subunit. J Biol Chem274: 30799-30810.
63.
Edwards E., Hampton E., Ashby CR, Zhang J., Wang RY ( 1996) 5-HT3-like receptors in the rat medial prefrontal cortex: further pharmacological characterization. Brain Res733: 21-30.
64.
Eisensamer B., Rammes G., Gimpl G., et al. (2003) Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor. Mol Psychiatr8: 994-1007.
65.
Eisensamer B., Uhr M., Meyr S., et al. (2005) Antidepressants and antipsychotic drugs colocalize with 5-HT3 receptors in raft-like domains. J Neurosci25: 10198-10206.
66.
Epstein SA, Kay G., Clauw D., et al. (1999) Psychiatric disorders in patients with fibromyalgia A multicenter investigation. Psychosomatics40: 57-63.
67.
Fan P. ( 1994a) Inhibition of a 5-HT3 receptor-mediated current by the selective serotonin uptake inhibitor, Fluoxetine. Neurosci Lett173: 210-212.
68.
Fan P. ( 1994b) Effects of antidepressants on the inward current mediated by 5-HT3 receptors in rat nodose ganglion neurons. Brit J Pharmacol112: 741-744.
69.
Fan P. ( 1994c) Facilitation of 5-hydroxytryptamine3 receptor desensitization by fluoxetine. Neuroscience62: 515-522.
70.
Färber L., Haus U., Späth M., Drechsler S. ( 2004) Physiology and pathophysiology of the 5-HT3 receptor . Scand J Rheumatol119: 2-8.
71.
Faris PL, Eckert ED, Kim SW, et al. (2006) Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms. J Affect Disorders92: 79-90.
72.
Faris PL, Kim SW, Meller WH, et al. (2000) Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomized, double-blind trial. Lancet355: 792-797.
73.
Fawcett J., Barkin RL ( 1998) Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression. J Affect Disorders51: 267-285.
74.
Fernandez HH, Trieschmann ME, Friedman JH ( 2003) Treatment of psychosis in Parkinson’s disease: safety considerations. Drug Safety26: 643-659.
75.
Fietta P., Manganelli P. ( 2007) Fibromyalgia and psychiatric disorders. Acta Bio-medica78: 88-95.
76.
Fletcher S., Barnes NM ( 1996) Distribution and characterisation of the [3H](S)-zacopride labelled 5-HT3 receptor in pig forebrain. Brain Res729: 281-284.
Fletcher S., Barnes NM ( 1999) Autoradiographic localization of the [3H]-(S)-zacopride labelled 5-HT3 receptor in porcine brain. Neurosci Lett269: 91-94.
79.
Fonseca MI, Ni YG, Dunning DD, Miledi M. ( 2001) Distribution of serotonin 2A, 2C and 3 receptor mRNA in spinal cord and medulla oblongata. BrainRes. Mol Brain Res89: 11-19.
80.
Frank B., Niesler B., Nöthen MM, et al. (2004) Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients. Am J Med Genet B, Neuropsychiatr Genet131: 1-5.
81.
Friedberg G., Zoldan J., Weizman A., Melamed E. ( 1998) Parkinson Psychosis Rating Scale: a practical instrument for grading psychosis in Parkinson’s disease. Clin Neuropharmacol21: 280-284.
82.
Gaddum JH, Picarelli ZP ( 1957) Two kinds of tryptamine receptor. Brit J Pharm Chemoth12: 323-328.
83.
Galzin AM, Poncet V., Langer SZ ( 1990) 5-HT3 receptor agonists enhance the electrically-evoked release of [3H]-5-HT in guinea-pig frontal cortex slices. Brit J Pharmacol101: 307P.
84.
Gehlert DR, Gackenheimer SL, Wong DT, Robertson DW ( 1991) Localization of 5-HT3 receptors in the rat brain using [3H] LY278584. Brain Res553: 149-154.
85.
Geurts FJ, De Schutter E., Timmermans JP ( 2002) Localization of 5-HT2A, 5-HT3, 5-HT5A and 5-HT7 receptor-like immunoreactivity in the rat cerebellum. J Chem Neuroanat24: 65-74.
86.
Gilon P., Yakel JL ( 1995) Activation of 5-HT3 receptors expressed in Xenopus oocytes does not increase cytoplasmic Ca2+ levels. Receptor Channel3: 83-88.
87.
Giovannini MG, Ceccarelli I., Molinari B., Cecchi M., Goldfarb J., Blandina P. ( 1998) Serotonergic modulation of acetylcholine release from cortex of freely moving rats. J Pharmacol Exp Ther285: 1219-1225.
88.
Göthert M. ( 1990) Presynaptic serotonin receptors in the central nervous system. Ann NY Acad Sci604: 102-112 .
89.
Grady TA, Broocks A., Canter SK, et al. (1996) Biological and behavioural responses to D-amphetamine, alone and in combination with the serotonin-3 receptor antagonist ondansetron, in healthy volunteers. Psychiat Res64: 1-10.
90.
Green T., Stauffer KA, Lummis SC ( 1995) Expression of recombinant homo-oligomeric 5-hydroxytryptamine3 receptors provides new insights into their maturation and structure. J Biol Chem270: 6056-6061 .
91.
Greenshaw AJ ( 1993) Behavioural pharmacology of 5-HT3 receptor antagonist: A critical update on therapeutic potential. Trends Pharmacol Sci141: 265-270.
92.
Grunes MS, Yaryura-Tobias JA, Neziroglu FA ( 1996) Ondansetron in social phobia. Biol Psychiat39: 624.
93.
Gum AM, Cheavens JS ( 2008) Psychiatric comorbidity and depression in older adults . Curr Psychiatry Rep10: 23-29.
94.
Guo W., Todd K., Bourin M., Hascoet M., Kouadio F. ( 1996) Additive effects of glyburide and antidepressants in the forced swimming test: evidence for the involvement of potassium channel blockade . Pharmacol Biochem Be54: 725-730.
95.
Hagan RM, Butler A., Hill JM, Jordan CC, Ireland SJ, Tyers MB ( 1987) Effect of the 5-HT3 receptor antagonist, GR38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain. Eur J Pharmacol138: 303-305.
96.
Hagan RM, Jones BJ, Jordan CC, Tyers MB ( 1990) Effect of 5-HT3 receptor antagonists on responses to selective activation of mesolimbic dopaminergic pathways in the rat. Brit J Pharmacol99: 227-232.
97.
Harmer CJ, Reid CB, Ray MK, Goodwin GM, Cowen PJ ( 2006) 5HT3 antagonism abolishes the emotion potentiated startle effect in humans. Psychopharmacology186: 18-24.
98.
Haus U., Späth M., Färber L. ( 2004) Spectrum of use and tolerability of 5-HT3 receptor antagonists . Scand J Rheumatol119: 12-18 .
99.
Haus U., Varga B., Stratz T., Späth M., Müller W. ( 2000) Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain. Scand J Rheumatol113: 55-58 .
100.
Herzog DB, Keller MB, Sacks NR, Yeh CJ, Lavori PW ( 1992) Psychiatric comorbidity in treatment-seeking anorexics and bulimics. J Am Acad Child Psy31: 810-818.
101.
Hettema JM ( 2008) What is the genetic relationship between anxiety and depression? Am J Med Genet C, Semin Med Genet148: 140-146.
102.
Hewlett WA, Schmid SP, Salomon RM ( 2003) Pilot trial of ondansetron in the treatment of 8 patients with obsessive-compulsive disorder. J Clin Psychiat64: 1025-1030.
103.
Hope AG, Downie DL, Sutherland L., Lambert JJ, Peters JA, Burchell B. ( 1993) Cloning and functional expression of an apparent splice variant of the murine 5-HT3 receptor A subunit. Eur J Pharmacol245: 187-192.
104.
Hoyer D. ( 1990) Serotonin 5-HT3, 5-HT4, and 5-HT-M receptors. Neuropsychopharmacology3: 371-383.
105.
Hoyer D., Gozlan H., Bolanos F., Schechter LE, Hamon M. ( 1989) Interaction of psychotropic drugs with central 5-HT3 recognition sites: fact or artifact? Eur J Pharmacol171: 137-139.
106.
Hoyer D., Hannon JP, Martin GR ( 2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Be71: 533-554.
107.
Huang J., Spier AD, Pickel VM ( 2004) 5-HT3A receptor subunits in the rat medial nucleus of the solitary tract: subcellular distribution and relation to the serotonin transporter. Brain Res1028: 156-169.
108.
Imperato A., Puglisi-Allegra S., Zocchi A., Scrocco MG, Casolini P., Angelucci L. ( 1990) Stress activation of limbic and cortical dopamine release is prevented by ICS 205-930 but not by diazepam. Eur J Pharmacol175: 211-214.
109.
Invernizzi R., Pozzi L., Samanin R. ( 1995) Selective reduction of extracellular dopamine in the rat nucleus accumbens following chronic treatment with DAU6215, a 5-HT3 receptor antagonist. Neuropharmacology34: 211-215.
110.
Isenberg KE, Ukhun IA, Holstad SG, et al. (1993) Partial cDNA cloning and NGF regulation of a rat 5-HT3 receptor subunit. Neuroreport18: 121-124.
111.
Jackson MB, Yakel JL ( 1995) The 5-HT3 receptor channel. Annu Rev Physiol57: 447-468.
112.
Jacocks HMI, Cox BM ( 1992) Serotonin-stimulated release of [3H] dopamine via reversal of the dopamine transporter in rat striatum and nucleus accumbens: a comparison with release elicited by potassium, N-methyl-D-aspartic acid, glutamic acid and D-amphetamine. J Pharmacol Exp Ther262: 356-364.
113.
Jensen AA, Davies PA, Bräuner-Osborne H., Krzywkowski K. ( 2008) 3B but which 3B? And that’s just one of the questions: the heterogeneity of human 5-HT3 receptors. Trends Pharmacol Sci29: 437-444.
114.
Johnson BA ( 2000) Serotonergic agents and alcoholism treatment: rebirth of the subtype concept- an hypothesis. Alcohol Clin Exp Res24: 1597-1601.
115.
Johnson BA ( 2004) Role of the serotonergic system in the neurobiology of alcoholism: implications for treatment. CNS Drugs18: 1105-1118.
116.
Johnson BA, Ait-Daoud N., Elkashef AM, et al. (2008) A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of methamphetamine dependence. Int J Neuropsychop11: 1-14.
117.
Johnson BA, Ait-Daoud N., Ma JZ, Wang Y. ( 2003) Ondansetron reduces mood disturbance among biologically predisposed, alcohol-dependent individuals. Alcohol Clin Exp Res27: 1773-1779.
118.
Johnson BA, Cowen PJ ( 1993) Alcohol-induced reinforcement: Dopamine and 5-HT3 receptor interactions in animals and humans. Drug Develop Res30: 153-169.
119.
Johnson BA, Roache JD, Ait-Daoud N., et al. (2006) A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence. Drug Alcohol Depen84: 256-263.
120.
Johnson BA, Roache JD, Ait-Daoud N., Zanca NA, Velazquez M. ( 2002) Ondansetron reduces the craving of biologically predisposed alcoholics. Psychopharmacology160: 408-413.
121.
Jones BJ, Costall B., Domeney AM, et al. (1988) The potential anxiolytic activity of GR 38032F, a 5-HT3 receptor antagonist. Brit J Pharmacol93: 985-993.
122.
Kankaanpaa A., Meririnne E., Seppala T. ( 2002) 5-HT3 receptor antagonist MDL72222 attenuates cocaine- and mazindol-, but not methylphenidate induced neurochemical and behavioural effects in the rat. Psychopharmacology159: 341-350.
123.
Kenney C., Kuo SH, Jimenez-Shahed J. ( 2008) Tourette’s syndrome. Am Fam Physician77: 651-658.
124.
Kidd EJ, Laporte AM, Langlois X., et al. (1993) 5-HT3 receptors in the rat central nervous system are mainly located on nerve fibres and terminals. Brain Res612: 289-298.
125.
Kilpatrick GJ, Butler A., Burridge J., Oxford AW ( 1990) 1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist. Eur J Pharmacol182: 193-197.
126.
Kilpatrick GJ, Jones BJ, Tyers MB ( 1987) Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature330: 746-748.
127.
Kos T., Popik P., Pietraszek M., et al. (2006) Effect of 5-HT3 receptor antagonist MDL 72222 on behaviour induced by ketamine in rats and mice. Eur Neuropsychopharm16: 297-310 .
128.
Koulu M., Sjoholm B., Lappalainen J., Virtanen R. ( 1989) Effects of acute GR38032F (Ondansetron), a 5-HT3 receptor antagonist, on dopamine and serotonin metabolism in mesolimbic and nigrostriatal dopaminergic neurons. Eur J Pharmacol169: 321-324.
129.
Koyama S., Matsumoto N., Kubo C., Akaike N. ( 2000) Presynaptic 5-HT3 receptor-mediated modulation of synaptic GABA release in the mechanically dissociated rat amygdala neurons . J Physiol529: 373-383.
130.
Lankiewicz S., Lobitz N., Wetzel CHR, Rupprecht R., Gisselmann G., Hatt H. ( 1998) Molecular cloning, functional expression, and pharmacological characterization of 5-hydroxytryptamine3 receptor cDNA and its splice variants from guinea pig. Mol Pharmacol53: 202-212.
131.
Laporte AM, Koscielniak T., Ponchant M., Verge D., Hamon M., Gozlan H. ( 1992) Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I] iodo-zacopride and [3H] zacopride as radioligands . Synapse10: 271-281.
132.
Lecrubier Y., Puech AJ, Azcona A., Bailey PE, Lataste XA ( 1993) Randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder . Psychopharmacology112: 129-133.
133.
Livesey MR, Cooper MA, Deeb TZ, et al. (2008) Structural determinants of Ca2+ permeability and conduction in the human 5-hydroxytryptamine type3A receptor. J Biol Chem283: 19301-19313 .
134.
Lumia AR, Teicher MH, Salchli F., Ayers E., Possidente B. ( 1992) Olfactory bulbectomy as a model for agitated hyposerotonergic depression. Brain Res587: 181-185.
135.
Luscombe GP, Martin KF, Hutchins LJ, Gosden J., Heal DJ ( 1993) Mediation of the antidepressant-like effect of 8-OH-DPAT in mice by postsynaptic 5-HT1A receptors. Brit J Pharmacol108: 669-677.
136.
McBride WJ, Lovinger DM, Machu T., et al. (2004) Serotonin-3 receptors in the actions of alcohol, alcohol reinforcement, and alcoholism. Alcohol-Clin Exp Res28: 257-267.
137.
McCann UD, Morgan CM, Geraci M., Slate SO, Murphy DL, Post RM ( 1997) Effects of the 5-HT3 antagonist, ondansetron, on the behavioural and physiological effects of pentagastrin in patients with panic disorder and social phobia. Neuropsychopharmacology17: 360-369.
138.
McNeish CS, Svingos AL, Hitzemann R., Strecker RE ( 1993) The 5-HT3 antagonist zacopride attenuates cocaine-induced increases in extracellular dopamine in rat nucleus accumbens. Pharmacol Biochem Be45: 759-763.
139.
Mahesh R., Perumal RV, Pandi PV ( 2005) Cancer chemotherapy-induced nausea and vomiting: role of mediators, development of drugs and treatment methods. Die Pharmazie60: 83-96.
140.
Mahesh R., Rajkumar R., Minasri B., Perumal RV ( 2007) Potential antidepressants: pharmacology of 2-(4-methyl piperazin-1-yl)-1, 8-naphthyridine-3-carbonitrile in rodent behavioural models . Die Pharmazie12: 919-924.
141.
Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. ( 1991) Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science254: 432-437.
142.
Martin KF, Hannon S., Phillips I., Heal DJ ( 1992a) Opposing roles for 5-HT1B and 5-HT3 receptors in the control of 5-HT release in rat hippocampus in vivo. Brit J Pharmacol106: 139-142.
143.
Martin R., Gozlan H., Puech AJ ( 1992b) 5-HT3 receptor antagonists reverse helpless behaviour in rats. Eur J Pharmacol212: 73-78.
144.
Mascagni F., McDonald AJ ( 2007) A novel subpopulation of 5-HT type 3A receptor subunit immunoreactive interneurons in the rat basolateral amygdala. Neuroscience144: 1015-1024.
145.
Matsumoto M., Yoshioka M., Togashi H., Tochihara M., Ikeda T., Saito H. ( 1995) Modulation of norepinephrine release by serotonergic receptors in the rat hippocampus as measured by in vivo microdialysis. J Pharmacol Exp Ther272: 1044-1051.
146.
Maura G., Andrioli GC, Cavazzani P., Raiteri M. ( 1992) 5-Hydroxytryptamine-3 receptors sited on cholinergic axon terminals of human cerebral cortex mediate inhibition of acetylcholine release . J Neurochem58: 2334-2337.
147.
Miquel MC, Emerit MB, Gringrich JA, Nosjean A., Hamon M., el Mestikawy S. ( 1995) Developmental changes in the differential expression of two serotonin 5-HT3 receptor splice variants in the rat. J Neurochem65: 475-483.
148.
Miquel MC, Emerit MB, Nosjean A., Simon A., Rumajogee P., Brisorgueil MJ, Doucet E., Hamon M., Vergé D. ( 2002) Differential subcellular localization of the 5-HT3-As receptor subunit in the rat central nervous system. Eur J Neurosci15: 449-457.
149.
Mitchell EA, Pratt JA ( 1991) Neuroanatomical structures involved in the action of the 5-HT3 antagonist ondansetron: a 2-deoxyglucose autoradiographic study in the rat. Brain Res538: 289-294.
150.
Miyake A., Mochizuki S., Takemoto Y., Akuzawa S. ( 1995) Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol48: 407-416.
151.
Morales M., Battenberg E., Bloom FE ( 1998) Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol402: 385-401.
152.
Morales M., Wang SD ( 2002) Differential composition of 5-hydroxytryptamine3 receptors synthesized in the rat CNS and peripheral nervous system. J Neurosci22: 6732-6741.
153.
Nakagawa Y., Ishima T., Takashima T. ( 1998) The 5-HT3 receptor agonist attenuates the action of antidepressants in the forced swim test in rats. Brain Res786: 189-193.
154.
Nayak SV, Rondé P., Spier AD, Lummis SC, Nichols RA ( 2000) Nicotinic receptors colocalize with 5-HT3 serotonin receptors on striatal nerve terminals. Neuropharmacology39: 2681-2690.
155.
Newberry NR, Cheshire SH, Gilbert MJ ( 1991) Evidence that the 5HT3 receptors of the rat, mouse and guinea-pig superior cervical ganglion may be different. Brit J Pharmacol102: 615-620.
156.
Niesler B., Flohr T., Nöthen MM, et al. (2001) Association between the 5′ UTR variant C178T of the serotonin receptor gene HTR3A and bipolar affective disorder . Pharmacogenetics11: 471-475.
157.
Niesler B., Frank B., Kapeller J., Rappold GA ( 2003) Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene310: 101-111.
158.
Niesler B., Walstab J., Combrink S., et al. (2007) Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E. Mol Pharmacol72: 8-17.
159.
Nutt DJ, Stein DJ ( 2006) Understanding the neurobiology of comorbidity in anxiety disorders. CNS Spectr11: 13-20.
160.
Offenbaecher M., Glatzeder K., Ackenheil M. ( 1998) Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM. Z Rheumatol57: 94-96.
161.
Overstreet DH, Pucilowski O., Rezvani AH, Janowsky DS ( 1995) Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of Flinders Sensitive Line rats as an animal model of depression. Psychopharmacology121: 27-37.
162.
Palfreyman MG, Sorenson SM, Gittos MW, et al. (1996) Neurotherapeutic potential of 5-HT3 receptor antagonists. Eur Neuropsychopharm6: S4 .
163.
Parker RMC, Barnes JM, Ge J., Barber PC, Barnes NM ( 1996) Autoradiographic distribution of [3H]-(S)-zacopride labelled 5HT3 receptors in human brain. J Neurol Sci144: 119-127.
Peroutka SJ ( 1988b) Species variations in 5-HT3 recognition sites labeled by 3H-quipazine in the central nervous system. N-S Arch Pharmacol338: 472-475.
166.
Perry DC ( 1990) Autoradiography of [3H]quipazine in rodent brain . Eur J Pharmacol187: 75-85.
167.
Peters JA, Lambert JJ ( 1989) Electrophysiology of 5-HT3 receptors in neuronal cell lines. Trends Pharmacol Sci10: 172-175.
168.
Peters JA, Malone HM, Lambert JJ ( 1992) Recent advances in the electrophysiological characterization of 5-HT3 receptors. Trends Pharmacol Sci13: 391-397.
169.
Piche T., Vanbiervliet G., Cherikh F., et al. (2005) Effect of ondansetron, a 5-HT3 receptor antagonist, on fatigue in chronic hepatitis C: a randomised, double blind, placebo controlled study. Gut54: 1169-1173.
170.
Porras G., De Deurwaerdere P., Moison D., Spampinato U. ( 2003) Conditional involvement of striatal serotonin 3 receptors in the control of in vivo dopamine outflow in the rat striatum. Eur J Neurosci17: 771-781.
171.
Raiteri M., Paudice P., Vallebuona F. ( 1993) Release of cholecystokinin in the central nervous system . Neurochem Int22: 519-527.
172.
Ramamoorthy R., Radhakrishnan M., Borah M. ( 2008) Antidepressant-like effects of serotonin type-3 antagonist, ondansetron: an investigation in behaviour-based rodent models . Behav Pharmacol19: 29-40.
173.
Rammes G., Eisensamer B., Ferrari U., et al. (2004) Antipsychotic drugs antagonize human serotonin type 3 receptor currents in a noncompetitive manner. Mol Psychiatr9: 818.
174.
Rammes G., Rupprecht R., Ferrari U., Zieglgänsberger W., Parsons CG ( 2001) The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT3 receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. Neurosci Lett306: 81-84.
175.
Rasmussen K., Stockton ME, Czachura JF ( 1991) The 5-HT3 receptor antagonist zatosetron decreases the number of spontaneously active A10 dopamine neurons. Eur J Pharmacol205: 113-116.
176.
Redrobe JP, Bourin M. ( 1997) Partial role of 5-HT2 and 5-HT3 receptors in the activity of antidepressants in the mouse forced swimming test. Eur J Pharmacol325: 129-135.
177.
Redrobe JP, Pinot P., Bourin M. ( 1996) The effect of the potassium channel activator, cromakalim, on antidepressant drugs in the forced swimming test in mice. Fund Clin Pharmacol10: 524-528.
178.
Richardson BP, Engel G. ( 1986) The pharmacology and function of 5-HT receptors . Trends Neurosci9: 424-428.
179.
Richardson BP, Engel G., Donatsch P., Stadler PA ( 1985) Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature376: 126-131.
180.
Romach MK, Kaplan HL, Busto UE, Somer G., Sellers EM ( 1998) A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation. J Clin Psychopharm18: 121-131.
181.
Sambunaris A., Hesselink JK, Pinder R., Panagides J., Stahl SM ( 1997) Development of new antidepressants. J Clin Psychopharm58: 40-53.
182.
Santiago M., Machado A., Cano J. ( 1995) 5-HT3 receptor agonist induced carrier-mediated release of dopamine in rat striatum in vivo. Brit J Pharmacol116: 1545-1550.
183.
Sell LA, Cowen PJ, Robson PJ ( 1995) Ondansetron and opiate craving A novel pharmacological approach to addiction. Brit J Psychiat166: 511-514.
184.
Singer HS ( 2001) The treatment of tics. Curr Neurol Neurosci Rep1: 195-202.
185.
Sirota P., Mosheva T., Shabtay H., Giladi N., Korczyn AD ( 2000) Use of the selective serotonin3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia. Am J Psychiat157: 287-289.
186.
Smith WT, Londborg PD, Blomgren SL, Tollefson GD, Sayler ME ( 1999) Pilot study of zatosetron (LY277359) maleate, a 5-hydroxytryptamine-3 antagonist, in the treatment of anxiety. J Clin Psychopharm19: 125-131.
187.
Sudweeks SN, Hooft JA, Yakel JL ( 2002) Serotonin 5-HT3 receptors in rat CA1 hippocampal interneurons: functional and molecular characterization. J Physiol544: 715-726.
188.
Sugita S., Shen KZ, North RA ( 1992) 5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat amygdala. Neuron8: 199-203.
189.
Tecott LH, Maricq AV, Julius D. ( 1993) Nervous system distribution of the serotonin 5-HT3 receptor mRNA. P Natl Acad Sci USA90: 1430-1434.
190.
Thompson AJ, Lummis SC ( 2007) The 5-HT3 receptor as a therapeutic target. Expert Opin Ther Tar11: 527-540.
191.
Thompson AJ, Price KL, Reeves DC, Chan SL, Chau PL, Lummis SC ( 2005) Locating an antagonist in the 5-HT3 receptor binding site using modeling and radioligand binding. J Biol Chem280: 20476-20482 .
192.
Toren P., Laor N., Cohen DJ, Wolmer L., Weizman A. ( 1999) Ondansetron treatment in patients with Tourette’s syndrome. Int Clin Psychopharm14: 373-376.
193.
Toren P., Weizman A., Ratner S., Cohen D., Laor N. ( 2005) Ondansetron treatment in Tourette’s disorder: a 3-week, randomized, double-blind, placebo-controlled study. J Clin Psychiat66: 499-503.
194.
Turkel SB, Nadala JGB, Wincor MZ ( 2001) Possible serotonin syndrome in association with 5-HT3 antagonist agents. Psychosomatics42: 258-260.
195.
Turner TJ, Mokler DJ, Luebke JI ( 2004) Calcium influx through presynaptic 5-HT3 receptors facilitates GABA release in the hippocampus: in vitro slice and synaptosome studies. Neuroscience129: 703-718.
196.
Tzvetkov MV, Meineke C., Oetjen E., Hirsch-Ernst K., Brockmöller J. ( 2007) Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine. Gene386: 52-62.
197.
van Hooft JA, Vijverberg HPM ( 2000) 5-HT3 receptors and neurotransmitter release in the CNS: a nerve ending story? Trends Neurosci23: 605-610.
198.
Varea E., Blasco-Ibáñez JM , Gómez-Climent MA, et al. (2007) Chronic fluoxetine treatment increases the expression of PSA-NCAM in the medial prefrontal cortex. Neuropsychopharmacology32: 803-812.
199.
Waeber C., Dixon K., Hoyer D., Palacios JM ( 1988) Localisation by autoradiography of neuronal 5-HT3 receptors in the mouse CNS. Eur J Pharmacol151: 351-352.
200.
Werner P., Kawashima E., Reid J., et al. (1994) Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants. Brain Res Mol Brain Res26: 233-241.
201.
West R., Hajek P. ( 1996) Randomised controlled trial of ondansetron in smoking cessation. Psychopharmacology126: 95-96.
202.
White A., Corn TH, Feetham C., Faulconbridge C. ( 1991) Ondansetron in treatment of schizophrenia. Lancet337: 1173.
203.
Wilde MI, Markham A. ( 1996) Ondansetron A review of its pharmacology and preliminary clinical findings in novel applications. Drugs52: 773-794.
204.
Wolf H. ( 2000) Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists. Scand J Rheumatol113: 37-45 .
205.
Wolters EC ( 1999) Dopaminomimetic psychosis in Parkinson’s disease patients: diagnosis and treatment. Neurology52: S10-S13.
206.
Wozniak KM, Pert A., Linnoila M. ( 1990) Antagonism of 5-HT3 receptors attenuates the effects of ethanol on extracellular dopamine. Eur J Pharmacol187: 287-289.
207.
Yamada K., Hattori E., Iwayama Y., et al. (2006) Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression. Biol Psychiat60: 192-201.
208.
Yan D., Schulte MK, Bloom KE, White MM ( 1999) Structural features of the ligand-binding domain of the serotonin 5HT3 receptor. J Biol Chem274: 5537-5541 .
209.
Zhang ZJ, Kang WH, Li Q., Wang XY, Yao SM, Ma AQ ( 2006) Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study. Schizophr Res88: 102-110.
210.
Zoldan J., Friedberg G., Livneh M., Melamed E. ( 1995) Psychosis in advanced Parkinson’s disease: treatment with ondansetron, a 5-HT3 receptor antagonist. Neurology45: 1305-1308.
