JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chopin, P.
Right arrow Articles by Marien, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chopin, P.
Right arrow Articles by Marien, M.

Vol. 288, Issue 2, 798-804, February 1999

Effects of Alpha-2 Adrenoceptor Agonists and Antagonists on Circling Behavior in Rats with Unilateral 6-Hydroxydopamine Lesions of the Nigrostriatal Pathway

Philippe Chopin, Francis C. Colpaert and Marc Marien

Centre de Recherche Pierre Fabre, Cedex, France

The present study examined the influence of alpha-2 adrenoceptor ligands on circling behavior in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway. The alpha-2 adrenoceptor agonists, clonidine and UK 14304, inhibited both the ipsilateral rotation induced by the indirect dopaminergic agonist, methylphenidate, and the contralateral circling induced by the direct dopaminergic agonist, apomorphine. In contrast, the alpha-2 adrenoceptor antagonists, idazoxan and (±)-efaroxan, enhanced the circling induced by either methylphenidate or apomorphine. The facilitating activity of efaroxan was stereoselective because the (+)-enantiomer mimicked the effect of (±)-efaroxan, whereas the (-)-enantiomer was essentially inactive, thus indicating a mediation by alpha-2 adrenoceptors. Upon administration alone, the above-mentioned compounds did not modify spontaneous circling behavior, except for UK 14304, which decreased, and (+)-efaroxan, which slightly increased, the ipsilateral rotation. We conclude that activation and antagonism of alpha-2 adrenoceptors inhibit and enhance, respectively, the circling behavior evoked by both direct and indirect dopaminergic agonists. Although a modulation of dopamine release may be involved in some of these drug effects, the effects on apomorphine-induced circling indicate an influence of alpha-2 adrenoceptor compounds on nigrostriatal neurotransmission at sites downstream from the dopaminergic neurons themselves. These findings support the notion of a potential benefit of alpha-2 adrenoceptor antagonists in the treatment of Parkinson's disease.

0022-3565/99/2882-0798$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
N. P. Visanji, S. H. Fox, T. H. Johnston, M. J. Millan, and J. M. Brotchie
{alpha}1-Adrenoceptors Mediate Dihydroxyphenylalanine-Induced Activity in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Lesioned Macaques
J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 276 - 283.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
P. Belujon, E. Bezard, A. Taupignon, B. Bioulac, and A. Benazzouz
Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats
J. Neurosci., September 5, 2007; 27(36): 9595 - 9606.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
D Devos, P Krystkowiak, F Clement, K Dujardin, O Cottencin, N Waucquier, K Ajebbar, B Thielemans, M Kroumova, A Duhamel, et al.
Improvement of gait by chronic, high doses of methylphenidate in patients with advanced Parkinson's disease
J. Neurol. Neurosurg. Psychiatry, May 1, 2007; 78(5): 470 - 475.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
N. Turle-Lorenzo, B. Maurin, C. Puma, C. Chezaubernard, P. Morain, C. Baunez, A. Nieoullon, and M. Amalric
The Dopamine Agonist Piribedil with L-DOPA Improves Attentional Dysfunction: Relevance for Parkinson's Disease
J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 914 - 923.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. L. Lane, S. Cheetham, and P. Jenner
Dopamine Uptake Inhibitor-Induced Rotation in 6-Hydroxydopamine-Lesioned Rats Involves Both D1 and D2 Receptors but Is Modulated through 5-Hydroxytryptamine and Noradrenaline Receptors
J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1124 - 1131.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. J. Hansard, L. A. Smith, M. J. Jackson, S. C. Cheetham, and P. Jenner
Dopamine, but Not Norepinephrine or Serotonin, Reuptake Inhibition Reverses Motor Deficits in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Treated Primates
J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 952 - 958.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P. Chopin, F. C. Colpaert, and M. Marien
Effects of Acute and Subchronic Administration of Dexefaroxan, an alpha 2-Adrenoceptor Antagonist, on Memory Performance in Young Adult and Aged Rodents
J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 187 - 196.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. J. Millan, D. Cussac, G. Milligan, C. Carr, V. Audinot, A. Gobert, F.'o. Lejeune, J.-M. Rivet, M. Brocco, D. Duqueyroix, et al.
Antiparkinsonian Agent Piribedil Displays Antagonist Properties at Native, Rat, and Cloned, Human alpha 2-Adrenoceptors: Cellular and Functional Characterization
J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 876 - 887.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.