Research article summary (published 25 Nov 2008):

The effects of the selective 5-HT(2C) receptor antagonist SB 242084 on learned helplessness in male Fischer 344 rats.

Full Abstract

RATIONALE: Rats exposed to an uncontrollable stressor demonstrate a constellation of behaviors such as exaggerated freezing and deficits in shuttle box escape learning. These behaviors in rats have been called learned helplessness and have been argued to model human stress-related mood disorders. Learned helplessness is thought to be caused by hyperactivation of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) and a subsequent exaggerated release of 5-HT in DRN projection sites. Blocking 5-HT(2C) receptors in the face of an increase in serotonin can alleviate anxiety behaviors in some animal models. However, specific 5-HT receptor subtypes involved in learned helplessness remain unknown. OBJECTIVES: The current experiments tested the hypothesis that 5-HT(2C) receptor activation is necessary and sufficient for the expression of learned helplessness. RESULTS: The selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) administered i.p. to adult male Fischer 344 rats prior to shuttle box behavioral testing, but not before stress, blocked stress-induced deficits in escape learning but had no effect on the exaggerated shock-elicited freezing. The selective 5-HT(2C) receptor agonist CP-809101 was sufficient to produce learned helplessness-like behaviors in the absence of prior stress and these effects were blocked by pretreatment with SB 242084. CONCLUSIONS: Results implicate the 5-HT(2C) receptor subtype in mediating the shuttle box escape deficits produced by exposure to uncontrollable stress and suggest that different postsynaptic 5-HT receptor subtypes underlie the different learned helplessness behaviors.

Author information

Author/s: Strong, Paul V (PV); Greenwood, Benjamin N (BN); Fleshner, Monika (M);

Affiliation: Department of Integrative Physiology and the Center for Neuroscience, University of Colorado, Clare Small Room 104, Campus Box 354, Boulder, CO 80309, USA. paul.strong(-atsign-)colorado.edu

Grants: NIMH068283 (Agency:PHS HHS)

Journal and publication information

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

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

Reference: 2009-May; vol 203 (issue 4) : pp 665-75

Dates: Created 2009/03/30; Completed 2009/08/17;

PMID: 19037632, status: MEDLINE (last retrieval date: 8/21/2009, 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.

Aminopyridines - pharmacology Animals Anxiety - chemically induced; psychology Escape Reaction - drug effects Freezing Reaction, Cataleptic - drug effects Helplessness, Learned Indoles - pharmacology Injections, Intraperitoneal

Injections, Intraperitoneal Male Piperazines - pharmacology Pyrazines - pharmacology Rats Rats, Inbred F344 Receptor, Serotonin, 5-HT2C - agonists; antagonists & inhibitors Stress, Psychological - metabolism; psychology

Associated Chemicals: Aminopyridines (0) ; CP-809,101 (0) ; Indoles (0) ; Piperazines (0) ; Pyrazines (0) ; Receptor, Serotonin, 5-HT2C (0) ; SB 242084 (0)

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