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Journal of Pharmacology and Experimental Therapeutics

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OtherBEHAVIORAL PHARMACOLOGY

Neonatal Administration of the Selective Serotonin Reuptake Inhibitor Lu 10–134-C Increases Forced Swimming-Induced Immobility in Adult Rats: A Putative Animal Model of Depression?

H. H. Hansen, C. Sánchez and E. Meier
Journal of Pharmacology and Experimental Therapeutics December 1997, 283 (3) 1333-1341;
H. H. Hansen
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C. Sánchez
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E. Meier
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Abstract

Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10–134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5–15 mg/kg b.i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.

Footnotes

  • Send reprint requests to: Connie Sánchez, Department of Psychopharmacology, H. Lundbeck A/S, Ottiliavej 7, DK-2500 Copenhagen-Valby, Denmark.

  • Abbreviations:
    FST
    forced swimming test
    OFT
    open field test
    SIT
    social interaction test
    SSRI
    selective serotonin reuptake inhibitor
    5-HT
    serotonin (5-hydroxytryptamine)
    NA
    noradrenaline
    DA
    dopamine
    SAL1
    saline control group 1
    SAL2
    saline control group 2
    LU
    Lu 10–134-C [5-chloro-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-phthalan]
    8-OH-DPAT
    [2,3(n)-3H]-2-(N1,N1-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphtalene
    QNB
    [3H]quinuclicinyl benzilate
    REM
    rapid eye movement
    ANOVA
    analysis of variance
    l-5-HTP
    l-5-hydroxytryptophan
    • Received September 11, 1996.
    • Accepted July 30, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 283, Issue 3
1 Dec 1997
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OtherBEHAVIORAL PHARMACOLOGY

Neonatal Administration of the Selective Serotonin Reuptake Inhibitor Lu 10–134-C Increases Forced Swimming-Induced Immobility in Adult Rats: A Putative Animal Model of Depression?

H. H. Hansen, C. Sánchez and E. Meier
Journal of Pharmacology and Experimental Therapeutics December 1, 1997, 283 (3) 1333-1341;

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OtherBEHAVIORAL PHARMACOLOGY

Neonatal Administration of the Selective Serotonin Reuptake Inhibitor Lu 10–134-C Increases Forced Swimming-Induced Immobility in Adult Rats: A Putative Animal Model of Depression?

H. H. Hansen, C. Sánchez and E. Meier
Journal of Pharmacology and Experimental Therapeutics December 1, 1997, 283 (3) 1333-1341;
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