Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice.

Full Abstract

RATIONALE: A recent study suggested that selective serotonin reuptake inhibitors were inactive in 40-week-old male mice in the mouse forced swimming test, possibly because of alteration of 5-HT1 receptors. OBJECTIVES: The present study was aimed at investigating the action of various antidepressant drugs in 4- and 40-week-old male mice using the mouse forced swimming test and determining the involvement of 5-HT1A and 5-HT1B receptors mediating the effects. METHODS: Different classes of antidepressants [imipramine (tricyclic), maprotiline (noradrenline reuptake inhibitor), venlafaxine (mixed serotonin and noradrenaline reuptake inhibitors), fluvoxamine and sertraline (selective serotonin reuptake inhibitor)] were tested in the same randomised experimental session, alone and in combination with 5-HT1A and 5-HT1B receptor agonists [buspirone (partial 5-HT1A agonist), anpirtoline (5-HT1B agonist)] in the mouse forced swimming test. RESULTS: All antidepressants were found to be active in the mouse forced swimming test in 4-week-old mice and 40-week-old mice, with the exception of fluvoxamine in the 40-week-old mice. The anti-immobility effect after antidepressant administration was higher in 4-week-old male mice than in 40-week-old male mice. Venlafaxine is the most active antidepressant drug in 40-week-old mice. Prior administration of buspirone (0.06 mg/kg, i.p.) or anpirtoline (1 mg/kg, i.p.) enhanced the antidepressant-like effects in 4-week-old mice (except in the case of sertraline, 8 mg/kg). In elderly mice, only prior administration of buspirone enhanced the antidepressant-like effects of fluvoxamine. A neurochemical study showed that significantly higher serotonin and dopamine concentrations were found in 40-week-old control mice brains than 4-week-old control mice brains but that the noradrenaline concentration is higher in 4-week-old mice. CONCLUSION: Tricyclic, noradrenaline reuptake inhibitors and serotonin reuptake inhibitors are more active in 4-week-old mice than 40-week-old mice. Our results suggested that 5-HT1B receptors may be more altered than 5-HT1A receptors in 40-week-old mice.

Author information

Author/s: David, D J (DJ); Bourin, M (M); Hascoët, M (M); Colombel, M C (MC); Baker, G B (GB); Jolliet, P (P);

Affiliation: Neurobiologie de lánxiété, Faculté de Médecine, Nantes, France.

Journal and publication information

Publication Type: Comparative Study; Journal Article

Journal: Psychopharmacology (Psychopharmacology (Berl)), published in Germany. (Language: eng)

Reference: 2001-Feb; vol 153 (issue 4) : pp 443-9

Dates: Created 2001/03/12; Completed 2001/05/17; Revised 2006/11/15;

PMID: 11243491, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aging - psychology
Animals
Antidepressive Agents - pharmacology
Biogenic Monoamines - metabolism
Brain Chemistry - drug effects
Dose-Response Relationship, Drug
Immobilization

Immobilization
Male
Mice
Receptor, Serotonin, 5-HT1B
Receptors, Serotonin - drug effects; physiology
Receptors, Serotonin, 5-HT1
Swimming - psychology

Associated Chemicals: Antidepressive Agents (0) ; Biogenic Monoamines (0) ; Receptor, Serotonin, 5-HT1B (0) ; Receptors, Serotonin (0) ; Receptors, Serotonin, 5-HT1 (0)

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