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Type: Artigo de periódico
Title: Adaptations in nucleus accumbens circuitry during opioid withdrawal associated with persistence of noxious stimulus-induced antinociception in the rat
Author: Schmidt, BL
Tambeli, CH
Levine, JD
Gear, RW
Abstract: We studied adaptations in nucleus accumbens opioidergic circuitry mediating noxious stimulus-induced antinociception (NSIA) in rats withdrawing from chronic morphine administration. Although the magnitude of NSIA in withdrawing rats was similar to that observed in naive rats despite the tolerance of withdrawing rats to the antinociceptive effects of acutely administered morphine, the involvement of nucleus accumbens opioid receptors in NSIA in withdrawing rats was different from previous observations in both naive and tolerant rats. In withdrawing rats intra-accumbens administration of the mu-opioid receptor antagonist Cys(2), Tyr(3), Orn(5), Pen(7) amide (CTOP), but not the delta-receptor antagonist naltrindole, blocked NSIA. Both antagonists blocked NSIA in the naive state, but neither was effective in tolerant rats. Also, intra-accumbens administration of the mu-agonist [D-Ala(2), N-Me-Phe(4)-Gly(5)-ol]-enkephalin (DAMGO) alone was sufficient to induce antinociception in withdrawing rats, whereas a combination of both mu- and delta-receptor agonists (ie, DAMGO and D-Pen(25)-enkephalin [DPDPE], respectively) is required to induce antinociception in naive rats. The delta- agonist DPDPE was without effect in the withdrawing rat, alone or when combined with DAMGO. Thus, although the magnitude of NSIA does not differ significantly among the 3 states, it is mediated by both mu- and delta-receptors in the naive rat, mu- but not delta-receptors in the withdrawing rat, and neither receptor type in the morphine tolerant rat. These changes may result from different degrees of tolerance, with delta-receptors being the most sensitive; however, it is not known how these changes occur without affecting the magnitude of the resultant antinociception. (C) 2003 by the American Pain Society.
Subject: analgesia
delta-opioid receptor
mu-opioid receptor
Country: Escócia
Editor: Churchill Livingstone
Rights: fechado
Identifier DOI: 10.1054/jpai.2003.12
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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