Reciprocal effects of combined administration of serotonin,noradrenaline and dopamine reuptake inhibitors on serotonin and dopamine levels in the rat prefrontal cortex: the role of 5-HT 1A receptors
Restricted accessOtherFirst published online November, 2007
Reciprocal effects of combined administration of serotonin,noradrenaline and dopamine reuptake inhibitors on serotonin and dopamine levels in the rat prefrontal cortex: the role of 5-HT 1A receptors
The purpose of the present study was to examine, by in vivo microdialysis technique, the effects of triple acting monoamine reuptake inhibitors, constructed by combinations of a selective serotonin reuptake inhibitor citalopram with a noradrenaline/dopamine reuptake inhibitor methylphenidate and a serotonin/noradrenaline reuptake inhibitor venlafaxine with a dopamine reuptake inhibitor GBR12909, on extracellular levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in the prefrontal cortex (PFC) of anaesthetized rats. At the highest dose tested, adjunctive methylphenidate (10 mg/kg s.c.) to citalopram markedly attenuated by 63% the extracellular levels of 5-HT as compared to the levels induced by citalopram (5 mg/kg i.p.) alone, whereas the overall DA concentrations significantly increased to about 149% of those induced by methylphenidate alone. Similarly, the combination of venlafaxine with GBR12909 (10 mg/kg s.c.) caused a reduction of 5-HT levels to 66% of the levels induced by venlafaxine (10 mg/kg i.p.) alone, whereas the overall DA levels increased to 151% of the venlafaxine-treated group. The extracellular levels of NA were only marginally affected by the treatments with combined reuptake inhibitors compared to the effects induced by methylphenidate or venlafaxine alone. The modulatory effects of combined administration of the DA/NA reuptake inhibitors with the 5-HT reuptake inhibitors (citalopram and venlafaxine) on potentiation of DA and attenuation of 5-HT efflux were completely reversed by a pre-treatment with the 5-HT1A receptor antagonist WAY-100635. These findings suggest a crucial role played by the 5-HT1A receptors in balancing the reuptake inhibitory efficacy for the enhancement of 5-HT and DA transmission in the PFC by the drugs combining the reuptake inhibition of all three monoamines.
Adell A. , Castro E. , Celada P. , Bortolozzi A. , Pazos A. , Artigas F. (2005) Strategies for producing faster acting antidepressants . Drug Discov Today15: 578—585
2.
Amargós-Bosch M. , Bortolozzi A. , Puig M.V. , Serrats J. , Adell A. , Celada P. , Toth M. , Mengod G. , Artigas F. (2004) Co-expression and In Vivo interaction of Serotonin1A and Serotonin2A Receptors in Pyramidal Neurons of Prefrontal Cortex . Cerebral Cortex14: 281—299
3.
Ashby Cr Jr , Edwards E. , Wang R.Y. (1994) Electrophysiological evidence for a functional interaction between 5-HT1A and 5-HT2A receptors in the rat medial prefrontal cortex: an iontophoretic study . Synapse17: 173—181
4.
Baraban J.M. , Aghajanian G.K. (1980) Suppression of firing activity of 5-HT neurons in the dorsal raphe by alpha-adrenoceptor antagonists . Neuropharmacology19: 355—363
5.
Béïque J.C. , de Montigny C. , Blier P. , Debonnel G. (1999) Venlafaxine: discrepancy between in vivo 5-HT and NE reuptake blockade and affinity for reuptake sites . Synapse32: 198—211
6.
Béïque J.C. , Pierre Blier M.D. , de Montigny C. , Debonnel G. (2000) Potentiation by (-)pindolol of the activation of postsynaptic 5-HT1A receptors induced by venlafaxineNeuropsychopharmacology23: 294—306
7.
Beyer C.E. , Boikess S. , Luo B. , Dawson L.A. (2002) Comparison of the effects of antidepressants on norepinephrine and serotonin concentration in the rat frontal cortex:an in vivo microdialysis study . J Pharmacol16: 297—304
8.
Blier P. , de Montigny C. (1987) Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain . Synapse1: 470—480
9.
Bortolozzi A. , Artigas F. (2003) Control of 5-hydroxytryptamine release in the dorsal raphe nucleus by the noradrenergic system in rat brain. Role of alpha-adrenoceptors . Neuropsychopharmacology28: 421—434
10.
Bosker F.J. , Klompmakers A. , Westenberg H G M (1997) Postsynaptic 5-HT1A receptors mediate 5-hydroxytryptamine release in the amygdale through a feedback to the caudal linear raphe . Eur J Pharmacol333: 147—157
11.
Bosker F.J. , Cremers T I F H , Jongsma M.E. , Westerink B H C , Wikströmt H.V. and den Boer J.A. (2001) Acute and chonic effects of citalopram on postsynaptic 5-hydroxytryptamine1A receptor-mediated feedback: a microdialysis study in the amygdale . Journal of Neurochemistry76: 1645—1653 .
12.
Bymaster F.P. , Felder C.C. (2002) Role of the cholinergic muscarinic system in bipolar disorder and related mechanism of action of antipsychotic agents . Mol Psychiatry7 Suppl 1: S57—S63
13.
Carboni E. , Tanda G.L. , Frau R. , DiChiara G D. (1990) Blockade of the noradrenaline carrier increased extracellular dopamine concentrations in the prefrontal cortex: Evidence that dopamine is taken up in vivo by noradrenergic terminals . J Neurochem55: 1067—1070
14.
Ceci A. , Baschirotto A. , Borsini F. (1994) The inhibitory effect of 8-OH-DPAT on the firing activity of dorsal raphé serotoninergic neurons in rats is attenuated by lesion of the frontal cortex . Neuropharmacology33: 709—713
15.
Celada P. , Puig M.V. , Casanovas J.M. , Guillazo G. , Artigas F. (2001) Control of dorsal raphe serotonergic neurons by the medial prefrontal cortex: involvement of 5-HT1A, GABAA, and glutamate receptors . J Neurosci21: 9917—9929
16.
Dawson L.A. , Nguyen H.Q. , Geiger A. (1999) Effects of venlafaxine on extracellular concentration of 5-HT and noradrenaline in the rat frontal cortex: augmentation via 5-HT1A receptor antagonism . Neuropharmacology38: 1153—1163
17.
Diaz-Mataix L. , Artigas F. , Celada P. (2006) Activation of pyramidal cells in rat medial prefrontal cortex projecting to ventral tegmental area by a 5-HT1A receptor agonist . Eur Neuropsychopharmacol16: 288—296
18.
Diaz-Mataix L. , Scorza M.C. , Bortolozzi A. , Toth M. , Celada P. , Artigas F. (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action . J Neurosci25: 10831—10843
19.
Devoto P. , Flore G. , Pani L. , Gessa G.L. (2001) Evidence for co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex . Mol Psychiatry6: 657—664
20.
Engleman E.A. , Perry K.W. , Mayle D.A. , Wong D.T. (1995) Simultaneous increases of extracellular monoamines in microdialysates from hypothalamus of conscious rats by duloxetine, a dual serotonin and norepinephrine uptake inhibitor . Neuropsychopharmacology12: 287—295
21.
Ferraro L. , Fuxe K. , Agnati L. , Tanganelli S. , Tomasini M.C. , Antonelli T. (2005) Modafinil enhances the increase of extracellular serotonin levels induced by the antidepressant drugs fluoxetine and imipramine: a dual probe microdialysis study in awake rat . Synapse55: 230—241
22.
Frazer A. (1997) Pharmacology of antidepressants . J Clin Psychopharmacol17(Suppl 1): 2S—18S
23.
Gartside S.E. , Umbers V. , Hajos M. , Sharp T. (1995) Interaction between a selective 5-HT1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5- HT . Br J Pharmacol15: 1064—1070
24.
Gartside S.E. , Umbers V. , Sharp T. (1997) Inhibition of 5-HT cell firing in the DRN by non- selective 5-HT reuptake inhibitors: studies on the role of 5-HT1A autoreceptors and noradrenergic mechanisms . Psychopharmacology (Berl)130: 261—268
25.
Gwirtsman H.E. , Szuba M.P. , Toren L. , Feist M. (1994) The antidepressant response to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate . Psychopharmacol Bull30: 157—164
26.
Haddjeri N. , Lavoie N. , Blier P. (2004) Electrophysiological Evidence for the Tonic Activation of 5-HT1A Autoreceptors in the Rat Dorsal Raphe NucleusNeuropsychopharmacology29: 1800—1806
27.
Hajós M. , Hajós-Korecsok É. , Sharp T. (1999) Role of the medial prefrontal cortex in 5-HT1A receptor-induced inhibition of 5-HT neuronal activity in the rat . Br J Pharmacol126: 1741—1750
28.
Hajós M. , Gartside S.E. , Varga V. , Sharp T. (2003) In vivo inhibition of neuronal HT activity in the rat ventromedial prefrontal cortex by midbrainraphe nuclei: role of 5-HT1A receptors . Neuropharmacology45: 72—81
29.
Hertel P. , Nomikos G.G. , Svensson T.H. (1999) Idazoxan preferentially increases dopamine output in the rat medial prefrontal cortex at the nerve terminal level . Eur J Pharmacol371: 153—158
30.
Hjorth S. , Bengtsson H.J. , Milano S. , Lundberg J.F. , Sharp T. (1995) Studies on the role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release—I. BMY7378 and prazosin . Neuropharmacology34: 615—620
31.
Hyttel J. (1994) Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs) . Int Clin Psychopharmacol9 (Suppl 1) 19—26 (review)
32.
Ichikawa J. , Ishii H. , Bonaccorso S. , Fowler W.L. , O'Laughlin I A, Meltzer H Y (2001) 5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem76: 1521—1531
33.
Invernizzi R. , Belli S. , Samanin R. (1992) Citalopram's ability to increase the extracellular concentrations of serotonin in the dorsal raphe prevents the drug's effect in the frontal cortex . Brain Res584: 322—324
34.
Jankowski M.P. and Sesack S. (2004) Prefrontal cortical projections to the rat dorsal raphe nucleus: ultrastructural features and associations with serotonin and gamma amino acid neuronsJ Comp Neurol468: 518—529
35.
Kihara T. , Ikeda M. (1995) Effects of duloxetine, a new serotonin and norepinephrine uptake inhibitor, on extracellular monoamine levels in rat frontal cortex . J Pharmacol Exp Ther272: 177—183
36.
Klimek V. , Schenck J.E. , Han H. , Stockmeier C.A. , Ordway G.A. (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study . Biol Psychiatry52: 740—748
37.
Klint T. , Weikop P. (2004) Monoamine transporters as continuing targets for drug discovery in depression . Drug Discov Today: Therapeutic Strategies1: 111—116
38.
Lam R.W. , Hossie H. , Solomons K. , Yatham L.N. (2004) Citalopram and bupropion-SR: combining versus switching in patients with treatment-resistant depression . J Clin Psychiatry65: 337—340
39.
Lavretsky H. , Kumar A. (2001) Methylphenidate augmentation of citalopram in elderly depressed patients . Am J Geriatr Psychiatry9: 298—303
40.
Lavretsky H. , Kim M.D. , Kumar A. , Reynolds C.F. 3rd (2003) Combined treatment with methylphenidate and citalopram for accelerated response in the elderly: an open trial . J Clin Psychiatry64: 1410—1414
41.
Martín-Ruiz R. , Puig M.V. , Celada P. , Shapiro D.A. , Roth B.L. , Mengod G. , Artigas F. (2001) Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism . J Neurosci21: 9856—9866
42.
Masand P.S. , Anand V.S. , Tanquary J.F. (1998) Psychostimulant augmentation of second generation antidepressants: a case series. Depress Anxiety7: 89—91
43.
Millan M.J. , Gobert A. , Girardon S. , Dekeyne A. (1999) Citalopram elicits a discriminative stimulus in rats at a dose selectively increasing extracellular levels of serotonin vs. dopamine and noradrenaline . Eur J Pharmacol364: 147—50 .
44.
Millan M.J. , Dekeyne A. , Papp M. , La Rochelle C.D. , MacSweeny C. , Peglion J.L. , Brocco M. (2001) S33005, a novel ligand at both serotonin and norepinephrine transporters: II. Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine . J Pharmacol Exp Ther298: 581—591
45.
Millan M.J. (2004) The role of monoamines in the actions of established and “novel” antidepressant agents: a critical review . Eur J Pharmacol500: 371—384
46.
Millan M.J. (2005) Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies . Therapie60: 441—460
47.
Millan M.J. (2006) Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application . Pharmacol Ther110: 135—370
48.
Miner L.H. , Jedema H.P. , Moore F.W. , Blakely R.D. , Grace A.A. , Sesack S. (2006) Chronic stress increases the plasmalemmal distribution of the noradrenaline transporter and the coexpression of tyrosine hydroxylase in norepinephrine axons in the prefrontal cortexJ. Neuroscience26: 1571—1578
49.
Neumeister A. , Willeit M. , Praschak-Rieder N. , Asenbaum S. , Stastny J. , Hilger E. , Pirker W. , Konstantinidis A. , Kasper S. (2001) Dopamine transporter availability in symptomatic depressed patients with seasonal affective disorder and healthy controls . Psychol Med31: 1467—1473
50.
Ninan P.T. , Hassman H.A. , Glass S.J. , McManus F.C. (2004) Adjunctive modafinil at initiation of treatment with a selective serotonin reuptake inhibitor enhances the degree and onset of therapeutic effects in patients with major depressive disorder and fatigue . J Clin Psychiatry65: 414—420
51.
Papakostas G.I. , Petersen T.J. , Green C. , Iosifescu D.V. , Yeung A.S. , Nierenberg A.A. , Fava M. , Posternak M.A. (2005) A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic specialty clinic . Ann Clin Psychiatry17: 161—165
52.
Paxinos G. , Watson C. (1997) The Rat Brain in Stereotaxic Coordinates. Academic Press, New York
53.
Pompeiano M. , Palacios J.M. , Mengod G. (1992) Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding . J Neurosci12: 440—453
54.
Puig M.V. , Celada P. , Díaz-Mataix L. , Artigas F. (2003) In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors. Relationship to thalamocortical afferents . Cereb Cortex13: 1870—1882
55.
Puig M.V. , Artigas F. , Celada P. (2005) Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA . Cereb Cortex15: 1—14
56.
Romero L. , Artigas F. (1997) Preferential potentiation of the effects of serotonin uptake inhibitors by 5-HT1A receptor antagonists in the dorsal raphe pathway: role of somatodendritic autoreceptors . J Neurochem68: 2593—2603
57.
Roy A. ( 1988) Plasma HVA levels in depressed patients and controls . J Affect Disord14: 293—296
58.
Roy A. , Karoum F. , Pollack S. (1992) Marked reduction in indexes of dopamine metabolism among patients with depression who attempt suicide . Arch Gen Psychiatry49: 447—450
59.
Pudovkina O.L. , Cremers T.I. , Westerink B.H. (2003) Regulation of the release of serotonin in the dorsal raphe nucleus by alpha1 and alpha2 adrenoceptors . Synapse50: 77—82
60.
Sakaue M. , Somboonthum P. , Nishihara B. , Koyama Y. , Hashimoto H. , Baba A. , Matsuda T. (2000) Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex . Br J Pharmacol129: 1028—1034
61.
Sanchez C. , Hyttel J. (1999) Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding . Cell Mol Neurobiol19: 67—89
62.
Santana N. , Bortolozzi A. , Serrats J. , Mengod G. and Artigas F. (2004) Expressein of serotonin1A and serotonin 2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortexCerebral Cortex 14: 1100—1109
63.
Schwartz T.L. , Azhar N. , Cole K. , Hopkins G. , Nihalani N. , Simionescu M. , Husain J. , Jones N. (2004) An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy . J Clin Psychiatry65: 1223—1227
64.
Skolnick P. , Popik P. , Janowsky A. , Beer B. , Lippa A.S. (2003) “ Broad spectrum” antidepressants: is more better for the treatment of depression?Life Sci73: 3175—3179
65.
Sprouse J.S. , Aghajanian G.K. (1986) (-)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists . Eur J Pharmacol128: 295—298
66.
Sprouse J.S. , Aghajanian G.K. (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists . Synapse1: 3—9
67.
Sprouse J.S. , Aghajanian G.K. (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphé neurons . Neuropharmacology27: 707—715
68.
Stoll A.L. , Pillay S.S. , Diamond L. , Workum S.B. , Cole J.O. (1996) Methylphenidate augmentation of serotonin selective reuptake inhibitors: a case series. J Clin Psychiatry57: 72—76
69.
Svensson T.H. , Bunney B.S. , Aghajanian G.K. (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the alpha-adrenergic agonist clonidine . Brain Res92: 291—306
70.
Tanda G. , Carboni E. , Frau R. , Di Chiara G. (1994) Increase of extracellular dopamine in the prefrontal cortex: a trait of drugs with antidepressant potential?Psychopharmacology (Berl)115: 285—288
71.
Tao R. , Ma Z. , Auerbach S.B. (2000) Differential effect of local infusion of serotonin reuptake inhibitors in the raphe versus forebrain and the role of depolarization-induced release in increased extracellular serotonin . J Pharmacol Exp Ther294: 571—579
72.
Tremblay P. , Blier P. (2006) Catecholaminergic strategies for the treatment of major depression . Curr Drug Targets7: 149—158
73.
Weikop P. , Kehr J. , Scheel-Kruger J. (2004) The role of alpha1- and alpha2-adrenoreceptors on venlafaxine-induced elevation of extracellular serotonin, noradrenaline and dopamine levels in the rat prefrontal cortex and hippocampus . J Psychopharmacol18: 395—403
74.
Willner P. (1997) The mesolimbic dopamine system as a target for rapid antidepressant action . Int Clin Psychopharmacol12(Suppl 3): S7—S14
75.
Yamamoto B.K. , Novotney S. (1998) Regulation of extracellular dopamine by the norepinephrine transporter . J Neurochem71: 274—280
76.
Wedzony K. , Mackowiak M. , Fijal K. , Golembiowska K. (1996) Ipsapirone enhances the dopamine ouflow via 5-HT1A receptors in the rat prefrontal cortexEur J Pharmacol305: 73—78
