Skip to main content
Log in

Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants

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

Abstract

This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.

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.

Similar content being viewed by others

References

  • Abel EL (1991) Behavior and corticosteroid response of Maudsley reactive and nonreactive rats in the open field and forced swimming test. Physiol Behav 50:151–153

    Google Scholar 

  • Altmann J (1974) Observational study of behavior: sampling methods. Behaviour 49:227–267

    Google Scholar 

  • Armario A, Gavalda A, Marti O (1988) Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate. Eur J Pharmacol 158:207–212

    Google Scholar 

  • Bolden-Watson C, Richelson E (1993) Blockade by newly-developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 52:1023–1029

    Google Scholar 

  • Borsini F, Meli A (1988) Is the forced swimming test a suitable model for revealing antidepressant activity? Psychopharmacology 94:147–160

    Google Scholar 

  • Cervo L, Grignaschi G, Samanin R (1990) α2-Adrenoceptor blockade prevents the effect of desipramine in the forced swimming test. Eur J Pharmacol 175:301–307

    Google Scholar 

  • Cervo L, Grignaschi G, Rossi C, Samanin R (1991) Role of serotonergic neurons in the effect of sertraline in rats in the forced swimming test. Eur J Pharmacol 196:217–222

    Google Scholar 

  • Delgado PL, Price LH, Miller HL, Salomon RM, Licinio J, Krystal JH, Heninger GR, Charney DS (1991) Rapid serotonin depletion as a provocative challenge test for patients with major depression: relevance to antidepressant action and the neurobiology of depression. Psychopharmacol Bull 27:321–330

    Google Scholar 

  • Delgado PL, Miller HL, Salomon RM, Licinio J, Heninger GR, Gelenberg AJ, Charney DS (1993) Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants. Psychopharmacol Bull 29:389–396

    Google Scholar 

  • Detke MJ, Rickels M, Lucki I (1994) Differential behavioral responding to noradrenergic and serotonergic antidepressants in the forced swim test (FST). Soc Neurosci Abstr 20:385

    Google Scholar 

  • Detke MJ, Wieland S, Lucki I (1995) Blockade of the antidepressant-like effects of 8-OH-DPAT, buspirone and desipramine in the rat forced swim test by 5-HT1A receptor antagonists. Psychopharmacology (in press)

  • Dunbar, RIM (1976) Some aspects of research design and their implications in the observational study of behavior. Behaviour 58:78–98

    Google Scholar 

  • Gorka Z, Wojtasik E, Kwiatek H, Maj J (1979) Action of serotoninmimetics in the behavioral despair test in rats. Commun Psychopharmacol 3:133–136

    Google Scholar 

  • Hjorth S, Sharp T (1990) Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies. Life Sci 46:955–963

    Google Scholar 

  • Holland PC (1977) Conditioned stimulus as a determinant of the form of the Pavlovian conditioned response. J Exp Psychol [Anim Behav Proc] 3:77–104

    Google Scholar 

  • Holland PC (1986) Temporal determinants of occasion setting in feature-positive discriminations. Anim Learn Behav 14:111–120

    Google Scholar 

  • Kitada Y, Miyauchi T, Kanazawa Y, Nakamichi H, Satoh S (1983) Involvement ofα- andβ 1-adrenergic mechanisms in the immobility-reducing action of desipramine in the forced swimming test. Neuropharmacology 22:1055–1060

    Google Scholar 

  • Leger DW (1977) An empirical evaluation of instantaneous and one-zero sampling of chimpanzee behavior. Primates 18:387–393

    Google Scholar 

  • Lucki I, Ward HR, Frazer A (1989) Effect of 1-(m-chlorophenyl)-piperazine and 1-(m-trifluoromethylphenyl)-piperazine on locomotor activity. J Pharmacol Exp Ther 249:155–164

    Google Scholar 

  • Lucki I, Singh A, Kreiss DS (1994) Antidepressant-like behavioral effects of serotonin receptor agonists. Neurosci Biobehav Rev 18:85–95

    Google Scholar 

  • Maj J, Rogoz Z, Skuza G (1992) The effects of combined treatment with MK-801 and antidepressant drugs in the forced swimming test in rats. Pol J Pharmacol Pharm 44:217–226

    Google Scholar 

  • Marti J, Armario A (1993) Effects of diazepam and desipramine in the forced swimming test: influence of previous experience with the situation. Eur J Pharmacol 236:295–299

    Google Scholar 

  • Martin P, Bateson P (1993) Measuring behaviour: an introductory guide, 2nd edn. Cambridge University Press, New York: pp 90–91

    Google Scholar 

  • Naitoh H, Nomura S, Kunimi Y, Yamaoka K (1992) “Swimming-induced head twitching” in rats in the forced swimming test induced by overcrowding stress: a new marker in the animal model of depression? Keio J Med 41:221–224

    Google Scholar 

  • Nishimura H, Tsuda A, Oguchi M, Ida Y, Tanaka M (1988) Is immobility of rats in the forced swim test “behavioral despair” Physiol Behav 42:93–95

    Google Scholar 

  • Nixon MK, Hascoet M, Bourin M, Colombel MC (1994) Additive effects of lithium and antidepressants in the forced swimming test: further evidence for involvement of the serotoninergic system. Psychopharmacology 115:59–64

    Google Scholar 

  • Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Biobehav Rev 17:51–68

    Google Scholar 

  • Pare WP (1989a) “Behavioral despair” test predicts stress ulcer in WKY rats. Physiol Behav 46:483–487

    Google Scholar 

  • Pare WP (1989b) Stress ulcer susceptibility and depression in Wistar Kyoto (WKY) rats. Physiol Behav 46:993–998

    Google Scholar 

  • Pare WP (1992) Learning behavior, escape behavior, and depression in an ulcer susceptible rat strain. Integr Physiol Behav Sci 27:130–141

    Google Scholar 

  • Paul IA, Duncan GE, Kuhn C, Mueller RA, Hong J, Breese GR (1990) Neural adaptation in imipramine-treated rats processed in forced swim test: assessment of time course, handling, rat strain and amine uptake. J Pharmacol Exp Ther 252:997–1005

    Google Scholar 

  • Porsolt RD (1981) Behavioral despair. In: Enna SJ (ed) Antidepressants: neurochemical, behavioral, and clinical perspectives. Raven Press, New York, pp 121–139

    Google Scholar 

  • Porsolt RD (1990) Behavioral despair: present status and future perspectives. In: Leonard BE, Spencer PJ (eds) Antidepressants: thirty years on. CNS Publishers, London, pp 85–94

    Google Scholar 

  • Porsolt RD, Lenegre A (1992) Behavioral models of depression. In: Elliot JM, Heal DJ, Marsden CA (eds) Experimental approaches to anxiety and depression. Wiley, New York, pp 73–85

    Google Scholar 

  • Porsolt R, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Google Scholar 

  • Porsolt RD, Anton G, Deniel M, Jalfre M (1978) Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Google Scholar 

  • Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M (1979) Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 57:201–210

    Google Scholar 

  • Porsolt RD, Lenegre A, McArthur RA (1991) Pharmacological models of depression. In: Animal models in psychopharmacology, B. Olivier, J. Slangen and J. Mos (eds). Birkhäuser, Basel, pp 137–159

    Google Scholar 

  • Rhine RJ, Flanigon M (1978) An empirical comparison of one-zero, focal-animal, and instantaneous methods of sampling spontaneous primate social behavior. Primates 19:353–361

    Google Scholar 

  • Richelson E, Pfenning M (1984) Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake. Eur J Pharmacol 104:277–286

    Google Scholar 

  • Singh A, Andrews CM, Lucki, I (1993) Serotonergic and noradrenergic lesions do not abolish the behavioral effects of antidepressants in the forced swimming test. Soc Neurosci Abstr 19:1245

    Google Scholar 

  • Tyler S (1979) Time-sampling: a matter of convention. Anim Behav 27:801–810

    Google Scholar 

  • Wieland S, Lucki I (1990) Antidepressant-like activity of 5-HT1A agonists measured with the forced swim test. Psychopharmacology 101:497–504

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Detke, M.J., Rickels, M. & Lucki, I. Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121, 66–72 (1995). https://doi.org/10.1007/BF02245592

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02245592

Key words

Navigation