Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice
In: Drug and alcohol dependence, Jg. 104 (2009), Heft 1-2, S. 175-184
academicJournal
- print; 10; 1 p.1/4
Zugriff:
Dynorphin is the presumed endogenous ligand for the kappa-opioid receptor. The dynorphin gene may play a role in psychotropic agent-mediated behavioral changes via dopaminergic modulation. Therefore, in this study, possible involvement of the dynorphin gene in nalbuphine-mediated behavioral responses was examined using prodynorphin (Pdyn) gene knock-out (―/―) mice. Pdyn gene deficiency potentiates nalbuphine-induced behavioral sensitization of locomotor activity and accumbal c-Fos expression. Administration of nalbuphine induced a significant increase in the dialysate dopamine level in the nucleus accumbens. This increase was more pronounced in the Pdyn (―/―) mice than in the wild-type (WT) mice. In addition, Pdyn (―/―) mice were more vulnerable to the naloxone-precipitated withdrawal syndrome (i.e., teeth chattering, wet dog shakes, forepaw tremors, jumping, weight loss, and global withdrawal score) after repeated treatment with nalbuphine than the WT mice. Consistently, nor-binaltorphimine, a kappa-opioid receptor antagonist, significantly potentiated nalbuphine-induced behavioral effects in WT mice, whereas U-50488H, a kappa-opioid receptor agonist, significantly attenuated these changes in Pdyn (―/―) mice in a dose-dependent manner. Our data suggest that the kappa-opioid receptor/dynorphin system is specifically modulated in response to behavioral sensitization and withdrawal signs induced by nalbuphine.
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Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice
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Autor/in / Beteiligte Person: | SHIN, Eun-Joo ; JANG, Choon-Gon ; GUOYING, BING ; DAE HUN, PARK ; OH, Chang-Hyun ; KYO HWAN, KOO ; KI WAN, OH ; YAMADA, Kiyofumi ; NABESHIMA, Toshitaka ; KIM, Hyoung-Chun |
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Zeitschrift: | Drug and alcohol dependence, Jg. 104 (2009), Heft 1-2, S. 175-184 |
Veröffentlichung: | Shannon: Elsevier, 2009 |
Medientyp: | academicJournal |
Umfang: | print; 10; 1 p.1/4 |
ISSN: | 0376-8716 (print) |
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