Research article summary (published 13 Feb 2008):

Neurochemical responses to antidepressants in the prefrontal cortex of mice and their efficacy in preclinical models of anxiety-like and depression-like behavior: a comparative and correlational study.

Full Abstract

RATIONAL: Marble burying and forced swimming behavior are widely used and sensitive tests for identifying clinically effective antidepressant drugs, although the underlying neurobiology of these behaviors is not fully elucidated. OBJECTIVES: The objective of this study was to determine the relationship between the behavioral effects of antidepressant drugs and their ability to modulate extracellular neurotransmitter levels in the prefrontal cortex. MATERIALS AND METHODS: The effects of fluoxetine, fluvoxamine, citalopram, imipramine, and desipramine (0 to 60 mg/kg by oral gavage, except fluoxetine at 0 to 40 mg/kg) were studied independently in CD-1 mice in the marble-burying task, forced swim task and on extracellular concentrations of serotonin, norepinephrine, and dopamine in the prefrontal cortex by freely moving microdialysis. RESULTS: Fluvoxamine, fluoxetine, and citalopram all suppressed marble-burying behavior, but produced no change in immobility time in the forced swim test. In contrast, imipramine and desipramine suppressed both marble-burying behavior and increased swimming time in the forced swim test, although desipramine mildly suppressed locomotor activity at the maximal dose. Fluvoxamine, fluoxetine, and citalopram all increased extracellular levels of cortical serotonin. Desipramine and imipramine increased extracellular dopamine levels. Fluoxetine, desipramine, and imipramine increased extracellular norepinephrine levels. Correlational analysis revealed a positive correlation between efficacy of drugs in the forced swim test and cortical extracellular dopamine levels, whereas a positive correlation was found between efficacy in the marble-burying test and extracellular serotonin levels. CONCLUSIONS: Although marble burying and forced swimming behavior have strong predictive validity in tests of antidepressant action, each assay appears to be underpinned by entirely different neurochemical systems.

Author information

Author/s: Kobayashi, Tomohiro (T); Hayashi, Etsuko (E); Shimamura, Midori (M); Kinoshita, Mine (M); Murphy, Niall P (NP);

Affiliation: Department of Pharmacology, Tsukuba Research Laboratories, High Throughput Biology, Discovery Research, GlaxoSmithKline, 43 Wadai, Tsukuba, Ibaraki 300-4247, Japan. Tomohiro_Kobayashi2(-atsign-)nts.toray.co.jp

Journal and publication information

Publication Type: Comparative Study; Journal Article

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

Reference: 2008-May; vol 197 (issue 4) : pp 567-80

Dates: Created 2008/04/08; Completed 2008/08/29;

PMID: 18274731, 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.

Animals Antidepressive Agents - pharmacology Anxiety - physiopathology; psychology Behavior, Animal - drug effects; physiology Depression - physiopathology; psychology Disease Models, Animal Dopamine - metabolism Dose-Response Relationship, Drug Drug Evaluation, Preclinical Helplessness, Learned Male

Male Mice Motivation Motor Activity - drug effects Neurotransmitter Agents - metabolism Norepinephrine - metabolism Prefrontal Cortex - drug effects; physiopathology Serotonin - metabolism Statistics as Topic Stereotyped Behavior - drug effects; physiology Swimming

Associated Chemicals: Antidepressive Agents (0) ; Neurotransmitter Agents (0) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Dopamine (51-61-6)

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