Research article summary (published 29 Sep 2004):

Increased behavioural activity of rats in forced swimming test after partial denervation of serotonergic system by parachloroamphetamine treatment.

Full Abstract

The present study aimed at characterizing the effect of partial 5-HT denervation by parachloroamphetamine (PCA), a 5-HT selective neurotoxin, on forced swimming behaviour and monoamine levels in several rat brain regions. PCA was administered intraperitoneally in two independent experiments in doses of 2, 4 and 6 mg/kg and in doses 1, 2, 4 mg/kg, respectively. PCA (2 mg/kg) reduced immobility in the forced swimming test in the Experiment 1 and according to Experiment 2 this is explained by increased swimming time. Dose-dependent reductions in 5-HT and 5-HIAA levels were found in all brain regions studied, and the maximal effects were of a similar magnitude. In septum, the effect of PCA took more time to develop. The effects of the lowest dose of PCA suggest that the neurotoxin affects not only the dorsal raphe projection areas but also the fine axons which arise from the median raphe. alpha2-Adrenoceptors and beta-adrenoceptors in cerebral cortex were not affected by the PCA treatment. Binding affinity of the 5-HT(1A) receptors was higher after all doses of PCA. On the second exposure to the forced swimming the time spent in swimming was found to be negatively and the time spent in immobile posture positively correlated with serotonin turnover in frontal cortex. The time spent in struggling on the second exposure to test was found to be negatively correlated with KD of beta-adrenoceptor binding in cerebral cortex. These data suggest that partial 5-HT denervation with low doses of PCA, which elicits a specific pattern of neurodegeneration, results in an increased behavioural activity, and that the traditional interpretation of the measures in forced swimming test, despite of the test's predictive power in revealing antidepressants acting on monoaminergic systems, is not adequate for studies on the neurochemical basis of depression.

Author information

Author/s: Häidkind, Riina (R); Eller, Marika (M); Kask, Ants (A); Harro, Maarike (M); Rinken, Ago (A); Oreland, Lars (L); Harro, Jaanus (J);

Affiliation: Department of Psychology, University of Tartu, Tiigi 78, 50410 Tartu, Estonia.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neurochemistry international (Neurochem Int), published in England. (Language: eng)

Reference: 2004-Oct; vol 45 (issue 5) : pp 721-32

Dates: Created 2004/07/05; Completed 2004/09/16; Revised 2006/11/15;

PMID: 15234115, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: 18 Feb 2009 00:00:00)

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 Behavior, Animal - drug effects Biogenic Monoamines - metabolism Brain Chemistry - drug effects Denervation Depression - psychology Dopamine - metabolism Dose-Response Relationship, Drug Hydroxyindoleacetic Acid - metabolism Male Norepinephrine - metabolism

Norepinephrine - metabolism Rats Rats, Wistar Receptor, Serotonin, 5-HT1A - drug effects; metabolism Receptors, Adrenergic, alpha-2 - drug effects; metabolism Receptors, Adrenergic, beta - drug effects; metabolism Receptors, Serotonin - drug effects; metabolism Serotonin - metabolism; physiology Serotonin Agents - toxicity Swimming - psychology p-Chloroamphetamine - toxicity

Associated Chemicals: Biogenic Monoamines (0) ; Receptors, Adrenergic, alpha-2 (0) ; Receptors, Adrenergic, beta (0) ; Receptors, Serotonin (0) ; Serotonin Agents (0) ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Dopamine (51-61-6) ; Hydroxyindoleacetic Acid (54-16-0) ; p-Chloroamphetamine (64-12-0)

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