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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

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 ISI 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 ISI Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Schmidt, B. L. Articles by Gear, R. W. Search for Related Content PubMed PubMed Citation Articles by Schmidt, B. L. Articles by Gear, R. W.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 2002, 22(15):6773-6780

Altered Nucleus Accumbens Circuitry Mediates Pain-Induced Antinociception in Morphine-Tolerant Rats

Brian L. Schmidt^{1, 2, 3}, Claudia H. Tambeli^{2, 3, 7}, Justine Barletta^{2, 3}, Lei Luo^{2, 3}, Paul Green^{2, 3}, Jon D. Levine^{2, 3, 4, 5, 6}, and Robert W. Gear^{2, 3}

¹ Graduate Program in Oral Biology, ² Department of Oral and Maxillofacial Surgery, ³ National Institutes of Health Pain Center (University of California at San Francisco), Departments of ⁴ Anatomy and ⁵ Medicine, and ⁶ Division of Neuroscience, University of California, San Francisco, California 94143, and ⁷ Faculty of Dentistry of Piracicaba, University of Campinas, Campinas, Brazil, 13414900

We investigated the effect of chronic administration of morphine on noxious stimulus-induced antinociception (NSIA) produced by intraplantar capsaicin injection. In the untreated (naïve) rat, we previously found that NSIA depends on activation of dopamine, nicotinic acetylcholine, and µ- and -opioid receptors in nucleus accumbens. Rats chronically implanted with subcutaneous morphine pellets demonstrated tolerance to the antinociceptive effects of acute systemic morphine administration but did not show cross-tolerance to NSIA. Morphine pretreatment, however, significantly reduced NSIA dependence on intra-accumbens opioid receptors but not on dopamine or nicotinic acetylcholine receptors. As observed in naïve rats, intra-accumbens microinjection of either the dopamine receptor antagonist flupentixol or the nicotinic receptor antagonist mecamylamine blocked NSIA in rats tolerant to the antinociceptive effects of morphine, but, in contrast to naïve rats, intra-accumbens microinjection of either the µ-receptor antagonist Cys²,Tyr³,Orn⁵,Pen⁷ amide or the -receptor antagonist naltrindole failed to block NSIA. These findings suggest that although NSIA is dependent on nucleus accumbens opioid receptors in the naïve state, this dependence disappears in rats tolerant to the antinociceptive effects of morphine, which may account for the lack of NSIA cross-tolerance. In separate experiments, intra-accumbens extracellular dopamine levels were measured using microdialysis. Dopamine levels increased after either capsaicin or systemic morphine administration in naïve rats but only after capsaicin administration in morphine pretreated rats. Thus, intra-accumbens dopamine release paralleled antinociceptive responses in naïve and morphine pretreated rats.

Key words: nucleus accumbens; morphine; tolerance; antinociception; dopamine release; noxious stimulation; capsaicin; pain; analgesia; µ opioid receptors; opioid receptors; microdialysis; jaw-opening reflex

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22156773-08$05.00/0

This article has been cited by other articles:

				D. J. Scott, M. M. Heitzeg, R. A. Koeppe, C. S. Stohler, and J.-K. Zubieta Variations in the human pain stress experience mediated by ventral and dorsal Basal Ganglia dopamine activity. J. Neurosci., October 18, 2006; 26(42): 10789 - 10795. [Abstract] [Full Text] [PDF]

				J. E. Belforte and J. H. Pazo Striatal Inhibition of Nociceptive Responses Evoked in Trigeminal Sensory Neurons by Tooth Pulp Stimulation J Neurophysiol, March 1, 2005; 93(3): 1730 - 1741. [Abstract] [Full Text] [PDF]

				L. Becerra, M. Iadarola, and D. Borsook CNS Activation by Noxious Heat to the Hand or Foot: Site-Dependent Delay in Sensory But Not Emotion Circuitry J Neurophysiol, January 1, 2004; 91(1): 533 - 541. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help