Abstract
The novel tricyclic antidepressant drug tianeptine had an antidepressant-like effect on a rat model of depression based on the deficit in open field activity observed on the day after 2 h restraint. Thus, when tianeptine (10 mg/kg IP) was given 2 h after the end of the restraint to either untreated rats or to animals previously given 10 mg/kg of the drug per day for 13 days, then the deficit was opposed. Tianeptine, given acutely but not chronically, moderately enhanced the 5-HT1C receptor-dependent hypolocomotor effect ofm-chlorophenylpiperazine (mCPP) but did not alter other 5-HT1 receptor subtype-dependent behaviour. Acute but not chronic tianeptine also decreased 5-HT2 receptor-dependent body shakes induced by 5-hydroxytryptophan. Shakes induced by the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) were unaffected. The results are discussed in relation to the possible mechanism of antidepressant action of tianeptine.
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References
Arnt A, Hyttel J (1989) Facilitation of 8-OH-DPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI. Eur J Pharmacol 161:45–51
Backus LI, Sharp T, Grahame-Smith DG (1990) Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. Br J Pharmacol 100:793–799
Bedard P, Pycock CJ (1977) “Wet dog” shake behaviour in the rat: a possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16:663–670
Beer M, Kennett GA, Curzon G (1990) A single dose of 8-OH-DPAT reduces raphe binding of [3H]8-OH-DPAT and increases the effect of raphe stimulation on 5-HT metabolism. Eur J Pharmacol 178:179–188
Blier P, De Montigny L, Chaput Y (1987) Modification of the serotonin system by antidepressant treatments: implications for the therapeutic response in major depression. J Clin Psychopharmacol 7:24S-35S
Couet W, Girault J, Latrille F, Salvadori C, Fourtillan JB (1990) Kinetic profiles of tianeptine and its MC5 metabolite in plasma, blood and brain after single and chronic intraperitoneal administration in the rat. Eur J Drug Metab Pharmacokinet 15:69–74
Cowen PJ (1990) A role for 5-HT in the action of antidepressant drugs. Pharmacol Ther 46:43–51
Curzon G, Kennett GA, Sarna GS, Whitton PS (1991) The effect of tianeptine and other antidepressants on a rat model of depression. Br J Psychiatry (in press)
Deakin JFW (1989) 5-HT receptor subtypes in depression. In: Bevan P, Cools AR, Archer T, (eds) Behavioural pharmacology of 5-HT. L. Erlbaum, Hillsdale, New Jersey, pp 179–204
Defrance R, Marey C, Kamoun A (1988) Antidepressant and anxiolytic activities of tianeptine: an overview of clinical trials. Clin Neuropharmacology 11 [Suppl. 2]:S74-S82
Dourish CT, Hutson PH, Curzon G (1985) Low doses of the putative serotonin agonist 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology 86:197–204
Dourish CT, Kennett GA, Curzon G (1987) The 5-HT1A agonists 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rats. J Psychopharmacol 1:23–30
Fattaccini CM, Bolonos-Jimenez H, Gozlan H, Hamon M (1990) Tianeptine stimulates uptake of 5-hydroxytryptamine in vivo in the rat brain. Neuropharmacology 29:1–8
Glennon RA, McKenney JD, Lyon RA, Titeler M (1986) 5-HT1 and 5-HT2 binding characteristics of 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane analogues. J Med Chem 29:194–199
Goodwin GM, De Sonza RJ, Green AR (1987) Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT1A-receptor mediated hypothermia and serotonin syndrome produced by 8-OH-DPAT in the rat. Psychopharmacology 91:500–505
Guelfi JD, Pichot P, Dreyfus JF (1989) Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline. Neuropsychobiology 22:41–48
Heninger GR, Charney DS, Sternberg DE (1984) Serotonergic function in depression: prolactin response to intravenous tryptophan in depressed patients and healthy subjects. Arch Gen Psychiatry 41:398–402
Hutson PH, Dourish CT, Curzon G (1986) Neurochemical and behavioural evidence for mediation of the hyperphagic action of 8-OH-DPAT by 5-HT cell body autoreceptors. Eur J Pharmacol 129:347–352
Hutson PH, Dourish CT, Curzon G (1988) Evidence that the hypophagic response to 8-OH-DPAT is mediated by 5-HT1A receptors. Eur J Pharmacol 150:361–366
Hutson PH, Sarna GS, O'Connell MT, Curzon G (1989) Hippocampal 5-HT synthesis and release in vivo is decreased by infusion of 8-OH-DPAT into the nucleus raphe dorsalis. Neurosci Lett 100:276–280
Kato G, Weitsch AF (1988) Neurochemical profile of tianeptine, a new antidepressant drug. Clin Neuropharmacol 11 [Suppl. 2]:S43-S50
Kennett GA, Curzon G (1988) Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. Br J Pharmacol 94:137–147
Kennett GA, Dickinson SL, Curzon G (1985) Enhancement of some 5-HT dependent behavioural responses following repeated immobilization in rats. Brain Res 330:253–263
Kennett GA, Dourish CT, Curzon G (1987a) Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol 134:265–274
Kennett GA, Marcou M, Dourish CT, Curzon G (1987b) Single administration of 5-HT1A agonists decreases 5-HT1A presynaptic, but not postsynaptic receptor-mediated responses: relationship to antidepressant-like action. Eur J Pharmacol 138:53–60
Kennett GA, Dourish CT, Curzon G (1987c) 5-HT1B agonists induce anorexia at a postsynaptic site. Eur J Pharmacol 141:429–435
Marek GJ, Li AA, Seiden LS (1989) Evidence for involvement of 5-hydroxytryptamine, receptors in antidepressant-like drug effects on differential reinforcement of low rate 72-second behaviour. J Pharmacol Exp Ther 250:60–71
Mennini T, Mocaer E, Garratini S (1987) Tianeptine, a selective enhancer of serotonin uptake in rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 336:478–482
Pericic D, Manev H (1988) Behavioural evidence for simultaneous dual changes of 5-HT receptor subtypes. Life Sci 42:2593–2601
Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829
Poignant JC (1981) Etude pharmacologique d'un nouvel anti-depresseur: la tianeptine. In: Biological Psychiatry, Proc 3rd Congress of Biological Psychiatry. Elsevier, North Holland, pp 573–578
Sharp T, Bramwell SR, Clark D, Grahame-Smith DG (1989) In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity. J Neurochem 53:234–240
Tricklebank MD, Forler C, Fozard JR (1985a) Subtypes of the 5-HT receptor mediating the behavioural response to 5-methoxy-NN-dimethyltryptamine in the rat. Eur J Pharmacol 117:15–24
Tricklebank MD, Forler C, Fozard JR (1985b) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino) tetralin in the rat. Eur J Pharmacol 106:271–282
Van Praag HM (1982) Neurotransmitters and CNS disease: depression. Lancet 2:1259–1264
Whitton PS, Sarna GS, O'Connell MT, Curzon G (1991) The effect of the novel antidepressant tianeptine on 5-hydroxytryptamine concentration in rat hippocampal dialysates in vivo. Neuropharmacology 30:1–4
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Whitton, P.S., Sarna, G.S., Datla, K.P. et al. Effects of tianeptine on stress-induced behavioural deficits and 5-HT dependent behaviour. Psychopharmacology 104, 81–85 (1991). https://doi.org/10.1007/BF02244558
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DOI: https://doi.org/10.1007/BF02244558