Skip to main content
Log in

Acute and chronic treatment with 5-HT reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

This study investigated behavioural effects of very potent 5-HT reuptake inhibitors after acute treatment (cianopramine and citalopram), as well as after chronic treatment (cianopramine), in two behavioural models of anxiety: 1) the light/dark choice procedure in mice and 2) the elevated plus-maze test in rats. In addition, the responses of mice to novelty in a free exploration paradigm were assessed after acute administration of both drugs. A single injection of cianopramine or citalopram increased neophobic reactions in the free exploration test. Furthermore, these drugs increased the avoidance reaction to a brightly illuminated chamber in the light/dark choice procedure as well as to open arms in the elevated plus-maze test. In contrast, after chronic treatment (10 mg/kg IP, once daily for 21 days) of cianopramine, anxiogenic-like effects were no longer produced in the light/dark choice paradigm whereas in the elevated plus-maze test, anxiolytic-like effects appeared. These results shed more light on the 5-HT hypothesis of anxiety, insofar as the increased availability of 5-HT resulting here from reuptake inhibition seems to initially result in an increased emotional reactivity which, however, subsequently disappears during chronic treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adell A, Artigas F (1991) Differential effects of clomipramine given locally or systematically on extracellular 5-hydroxytryptamine in raphe nuclei and frontal cortex. An in vivo brain microdialysis study. Naunyn-Schmiedeberg's Arch Pharmacol 343:237–244

    Article  Google Scholar 

  • Åsberg M, Eriksson B, Måtensson B, Träskman-Bendz L, Wägner A (1986) Therapeutic effects of serotonin uptake inhibitors in depression. J Clin Psychiatry 47:23–35

    Google Scholar 

  • Belzung C, Misslin R, Vogel E, Dodd RH, Chapouthier G (1987) Anxiogenic effects of methyl-β-carboline in a light/dark choice situation. Pharmacol Biochem Behav 28:29–33

    Google Scholar 

  • Bodnoff SR, Suranyi-Cadotte B, Aitken DH, Quirion R, Meaney MJ (1988) The effects of chronic antidepressant treatment in an animal model of anxiety. Psychopharmacology 95:298–302

    Article  PubMed  Google Scholar 

  • Bodnoff SR, Suranyi-Cadotte B, Quirion R, Meaney MJ (1989) A comparison of the effects of diazepam versus several typical and atypical antidepressant drugs in an animal model of anxiety. Psychopharmacology 97:277–279

    Article  Google Scholar 

  • Cadogan AK, Wright IK, Coombs I, Marsden CA, Kendall DA, Tulloch I (1992) Repeated paroxetine administration in the rat produces an anxiolytic profile in the elevated X-maze and a decreased3H-ketanserin binding. Neurosci Lett 42:S8 (suppl)

    Google Scholar 

  • Chaput Y, de Montigny C, Blier P (1991) Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. Neuropsychopharmacology 5:219–229

    PubMed  Google Scholar 

  • Chopin P, Briley M (1987) Animal models of anxiety: the effects of compounds that modify 5-HT neurotransmission. TIPS 8:383–389

    Google Scholar 

  • Da Prada M, Keller HH, Burkard WP, Schaffner R, Bonetti EP, Launay JM, Haefely W (1982) Some neuropharmacological effects of Ro 11-2465 — a novel tricyclic antidepressant with potent inhibitory activity on the uptake of 5-HT. In: Advances in biochemical psychopharmacology vol 31 (Typical and atypical antidepressants: Molecular mechanisms) pp 235–248

  • File SE (1985) Animal models for predicting clinical efficacy of anxiolytic drugs: social behaviour. Neuropsychobiology 13:55–62

    PubMed  Google Scholar 

  • File SE, Bond AJ, Lister RJ (1982) Interaction between effects of caffeine and lorazepam in performance tests and self-ratings. J Clin Psychopharmacol 2:102–106

    PubMed  Google Scholar 

  • Fontana DJ, Carbary TJ, Commissaris RL (1989) Effects of acute and chronic anti-panic drug administration on conflict behavior in the rat. Psychopharmacology 98:157–162

    Google Scholar 

  • Giesecke ME (1990) Overcoming hypersensitivity to fluoxetine in a patient with panic disorder. Am J Psychiatry 147:532–533

    Google Scholar 

  • Goodmann WK, Price LH, Rasmussen SA, Charney DS, Woods SW, Heininger GR (1986) Evidence for abnormal serotonergic function in obsessive compulsive disorder. Neurosci Abstr 12:317.6

    Google Scholar 

  • Gorman JM, Liebowitz MR, Fyer AJ (1987) An open trial of fluoxetine in the treatment of panic attacks. J Clin Psychopharmacol 7:329–332

    PubMed  Google Scholar 

  • Griebel G, Saffroy-Spittler M, Misslin R, Vogel E, Martin JR (1990) Serenics fluprazine (DU 27716) and eltoprazine (DU 28853) enhance neophobic and emotional behaviour in mice. Psychopharmacology 102:498–502

    Google Scholar 

  • Griebel G, Misslin R, Pawlowski M, Vogel E (1991)m — Chlorophenylpiperazine enhances neophobic and anxious behaviour in mice. NeuroReport 2:627–629

    PubMed  Google Scholar 

  • Griebel G, Misslin R, Pawlowski M, Guardiola-Lemaître B, Guillaumet G, Bizot-Espiard J (1992) Anxiolytic-like effects of a selective 5-HT1A agonist, S20244, and its enantiomers in mice. NeuroReport 3:84–86

    PubMed  Google Scholar 

  • Handley SL, McBlane JW (1992) Opposite effects of fluoxetine in two animal models of anxiety. Br J Pharmacol 107:446P (suppl)

    Google Scholar 

  • Humble M, Koczkas C, Wistedt B (1989) Serotonin and anxiety: an open study of citalopram in panic disorder. In: Stefanis CN, Soldatos CR, Rabavilas AD (eds) Psychiatry today: VIII World Congress of Psychiatry Abstracts. Elsevier, New York, p 151

    Google Scholar 

  • Hyttel J (1977) Neurochemical characterization of a new potent and selective serotonin uptake inhibitor: Lu 10-171. Psychopharmacology 51:225–233

    Google Scholar 

  • Insel TR, Mueller EA, Alterman I, Linnoila M, Murphy DL (1985) Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry 20:1174–1188

    Article  PubMed  Google Scholar 

  • 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 Res 584:322–324

    Article  PubMed  Google Scholar 

  • Linnoila M, Eckhardt M, Durcan M, Lister R, Martin P (1987) Interactions of serotonin with ethanol: clinical and animal studies. Psychopharmacol Bull 23:452–457

    Google Scholar 

  • Maître L, Moser P, Baumann PA, Waldmeier PC (1980) Amine uptake inhibitors: criteria of selectivity. Acta Psychiatr Scand 61 [Suppl. 280]:97–110

    Google Scholar 

  • Maître L, Baumann PA, Jaekel J, Waldmeier PC (1982) 5-HT uptake inhibitors: psychopharmacological and neurobiochemical criteria of selectivity. Adv Biochem Psychopharmacol 34 [Serotonin in biological psychiatry]:229–246

    Google Scholar 

  • Maj J, Moryl E (1992) Effects of sertraline and citalopram given repeatedly on the responsiveness of 5-HT receptor subpopulations. J Neural Transm [GenSect] 88:143–156

    Article  PubMed  Google Scholar 

  • Montgomery SA (1991) Clinical significance of 5-HT uptake inhibitors. Hum Psychopharmacol 6:S3-S7

    Google Scholar 

  • Pawlowski L, Kwiatek H, Górka Z (1981) Is Ro 11-2465 (cyanimipramine) an antagonist of postsynaptic serotonin receptors? J Neural Transm 52:61–72

    Article  PubMed  Google Scholar 

  • Pawlowski L, Nowak G, Górka Z, Mazela H (1985) Ro 11-2465 (cyan-imipramine), citalopram and theirN-desmethyl metabolites: effects on the uptake of 5-hydroxytryptamine and noradrenaline in vivo and related pharmacological activities. Psychopharmacology 86:156–163

    Google Scholar 

  • Pellow S (1986) Anxiolytic and anxiogenic drug effects in a novel test of anxiety: are exploratory models of anxiety in rodents valid? Methods Find Exp Clin Pharmacol 8:557–565

    PubMed  Google Scholar 

  • Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529

    Article  PubMed  Google Scholar 

  • Pellow S, Johnston AL, File SE (1987) Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat. J Pharm Pharmacol 39:917–928

    PubMed  Google Scholar 

  • Rago L, Kiivet RA, Harro J, Pold M (1988) Behavioral differences in an elevated plus-maze: correlation between anxiety and decreased number of GABA and benzodiazepine receptors in mouse cerebral cortex. Naunyn-Schmiedeberg's Arch Pharmacol 337:675–678

    Google Scholar 

  • Saletu B, Grünberger J (1985) Classification and determination of cerebral bioavailability of fluoxetine: pharmacokinetic, pharmaco-EEG and psychometric analyses. Clin Psychiatry 46:45–52

    Google Scholar 

  • Treit D (1991) Anxiolytic effects of benzodiazepines and 5-HT1A agonists: animal models. In: Rodgers RJ, Cooper SJ (eds) 5-HT1A agonists, 5-HT3 antagonists and benzodiazepines: their comparative behavioural pharmacology. Wiley, Chichester, pp 107–131

    Google Scholar 

  • Van Praag HM (1988) Serotonin disturbances in psychiatric disorders: functional versus nosological interpretation. Adv Biol Psychiatry 17:52–57

    Google Scholar 

  • Westenberg HGM (1992) Serotonin in anxiety and related disorders. 2nd International Symposium on Serotonin, Houston, September 15–18, p 24 (abstract)

  • Westenberg HGM, den Boer JA (1988) Clinical and biochemical effects of selective serotonin-uptake inhibitors in anxiety disorders. Adv Biol Psychiatry 17:84–99

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Griebel, G., Moreau, JL., Jenck, F. et al. Acute and chronic treatment with 5-HT reuptake inhibitors differentially modulate emotional responses in anxiety models in rodents. Psychopharmacology 113, 463–470 (1994). https://doi.org/10.1007/BF02245224

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245224

Key words

Navigation