Research article summary (published 22 Jul 2009):

Marked behavioral activation from inhibitory stimulation of locus coeruleus alpha1-adrenoceptors by a full agonist.

Full Abstract

alpha(1)-Adrenoceptors are concentrated in the locus coeruleus (LC) where they appear to regulate various active behaviors but have been difficult to stimulate effectively. The present study examined the behavioral, pharmacological and neural effects of possible stimulation of these receptors with 6-fluoronorepinephrine (6FNE), the only known selective alpha-agonist that has full efficacy at all brain alpha-receptors. Infusion of this compound in the mouse LC was found to produce extreme activation of diverse motivated behaviors of exploration, wheel-running and operant approach responding in different environments consistent with a global behavioral function of the dorsal noradrenergic system. Infusion of selective antagonists of alpha(1)- (terazosin) or alpha(2)- (atipamezole) receptors or of either the partial alpha(1)-agonist, phenylephrine, or full alpha(2)-agonist, dexmedetomidine, indicated that the behavioral effects of 6FNE were due largely due to activation of LC alpha(1)-receptors consistent with the known greater density of alpha(1)- than alpha(2)-adrenoreceptors in the mouse nucleus. Immunohistochemistry of fos in tyrosine hydroxylase-positive LC neurons following IV ventricular infusions indicated that 6FNE markedly depressed whereas terazosin strongly enhanced the apparent functional activity of the nucleus. The changes in fos expression following 6FNE and terazosin were significantly greater than those following dexmedetomidine and atipamezole. It is hypothesized that the alpha(1)-receptors of the mouse LC are strongly activated by 6FNE and serve to potently inhibit its tonic or stress-induced activity which in turn disinhibits prepotent motivated behaviors.

Author information

Author/s: Stone, Eric A (EA); Lin, Yan (Y); Sarfraz, Yasmeen (Y); Quartermain, David (D);

Affiliation: Department of Psychiatry, New York University Langone School of Medicine, 550 First Ave, New York, NY 10016, USA. eric.stone(-atsign-)nyumc.org

Grants: 5R01 MH045265 (Agency:NIMH NIH HHS) ; M0 RR00096 (Agency:NCRR NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Brain research (Brain Res), published in Netherlands. (Language: eng)

Reference: 2009-Sep; vol 1291 (issue ) : pp 21-31

Dates: Created 2009/08/31; Completed 2009/11/04;

PMID: 19632210, status: MEDLINE (last retrieval date: 11/4/2009, 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.

Adrenergic alpha-Agonists - pharmacology Adrenergic alpha-Antagonists - pharmacology Analysis of Variance Animals Catheters, Indwelling Conditioning, Operant - drug effects Exploratory Behavior - drug effects Fluorescent Antibody Technique Locus Coeruleus - drug effects; physiology

Male Mice Motor Activity - drug effects Neurons - metabolism Oxidopamine - toxicity Proto-Oncogene Proteins c-fos - metabolism Receptors, Adrenergic, alpha-1 - physiology Receptors, Adrenergic, alpha-2 - physiology Tyrosine 3-Monooxygenase - metabolism

Associated Chemicals: Adrenergic alpha-Agonists (0) ; Adrenergic alpha-Antagonists (0) ; Proto-Oncogene Proteins c-fos (0) ; Receptors, Adrenergic, alpha-1 (0) ; Receptors, Adrenergic, alpha-2 (0) ; Oxidopamine (1199-18-4) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)

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