QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 22, 2004, 24(38):8193-8197; doi:10.1523/JNEUROSCI.1657-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Xu, G.-P. Articles by Valentino, R. J. Search for Related Content PubMed PubMed Citation Articles by Xu, G.-P. Articles by Valentino, R. J.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Chronic Morphine Sensitizes the Brain Norepinephrine System to Corticotropin-Releasing Factor and Stress

Guang-Ping Xu,¹ Elisabeth Van Bockstaele,² Beverly Reyes,² Thelma Bethea,¹ and Rita J. Valentino¹

¹Departments of Pediatrics and Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, and ²Department of Neurosurgery, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania 19107

Chronic opiate use produces persistent changes in brain neurons that are expressed as adverse effects, including physical dependence and compulsive drug-seeking behavior. Dysregulation of the hypothalamic-pituitary-adrenal response to stress also occurs with chronic opiate administration and has been implicated as a contributing factor to continued substance abuse. This study provides the first evidence for dysregulation of the central noradrenergic response to stress by chronic opiates. Chronic morphine selectively sensitized locus ceruleus (LC)-norepinephrine (NE) neurons to corticotropin-releasing factor (CRF), an integral mediator of the stress response. CRF doses that were inactive in vehicle-treated rats produced a near-maximal activation of LC neurons of rats chronically administered morphine. LC sensitization to CRF was not solely a pharmacological phenomenon but was expressed as hyperresponsivity to physiological stress. Finally, opiate-induced LC sensitization translated to a change in the behavioral repertoire in response to environmental stress (swim stress) such that NE-mediated hyperactive behaviors predominated. The opiate-induced sensitization of the central NE response to stress predicts that chronic opiate administration increases vulnerability to certain stress-related symptoms (e.g., hyperarousal, attentional dysfunction), and this may contribute to the maintenance of opiate-seeking behavior.

Key words: corticotropin-releasing factor; locus ceruleus; morphine; µ-opiate receptor; swim stress; 8-bromo-cAMP

---

Received May 2, 2004; revised July 9, 2004; accepted August 10, 2004.

This article has been cited by other articles:

				R. Pastor, C. S. McKinnon, A. C. Scibelli, S. Burkhart-Kasch, C. Reed, A. E. Ryabinin, S. C. Coste, M. P. Stenzel-Poore, and T. J. Phillips From the Cover: Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: A urocortin1-independent mechanism PNAS, July 1, 2008; 105(26): 9070 - 9075. [Abstract] [Full Text] [PDF]

				A. Kreibich, B. A. S. Reyes, A. L. Curtis, L. Ecke, C. Chavkin, E. J. V. Bockstaele, and R. J. Valentino Presynaptic Inhibition of Diverse Afferents to the Locus Ceruleus by {kappa}-Opiate Receptors: A Novel Mechanism for Regulating the Central Norepinephrine System J. Neurosci., June 18, 2008; 28(25): 6516 - 6525. [Abstract] [Full Text] [PDF]

				B. A. S. Reyes, R. J. Valentino, and E. J. Van Bockstaele Stress-Induced Intracellular Trafficking of Corticotropin-Releasing Factor Receptors in Rat Locus Coeruleus Neurons Endocrinology, January 1, 2008; 149(1): 122 - 130. [Abstract] [Full Text] [PDF]

				B. Boutrel, P. J. Kenny, S. E. Specio, R. Martin-Fardon, A. Markou, G. F. Koob, and L. de Lecea Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior PNAS, December 27, 2005; 102(52): 19168 - 19173. [Abstract] [Full Text] [PDF]

				J. Liu, B. Yu, L. Orozco-Cabal, D. E. Grigoriadis, J. Rivier, W. W. Vale, P. Shinnick-Gallagher, and J. P. Gallagher Chronic Cocaine Administration Switches Corticotropin-Releasing Factor2 Receptor-Mediated Depression to Facilitation of Glutamatergic Transmission in the Lateral Septum J. Neurosci., January 19, 2005; 25(3): 577 - 583. [Abstract] [Full Text] [PDF]

				H. P. Jedema and A. A. Grace Corticotropin-Releasing Hormone Directly Activates Noradrenergic Neurons of the Locus Ceruleus Recorded In Vitro J. Neurosci., October 27, 2004; 24(43): 9703 - 9713. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help