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• W1994004692 abstract "We investigated how dizocilpine, a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, affects the development of morphine dependence in mice. Co-administration of dizocilpine (0.25 mg/kg) and morphine (10 mg/kg) for 5 days attenuated the development of tolerance to the antinociceptive effects of morphine. The withdrawal manifestation induced by the naloxone-challenge (5 mg/kg) was significantly reduced in mice that were treated with a combination of dizocilpine and morphine, compared to the mice treated with morphine and saline. The present study revealed a significant increase in c-Fos protein expression in the cortex and thalamus of mice showing naloxone-precipitated withdrawal syndrome. The combination of dizocilpine and morphine prevented the increase of c-Fos protein expression in the cortex and thalamus. Interestingly, repeated co-administration of dizocilpine and morphine prevented the withdrawal-induced phosphorylation of Ca2+/calmodulin kinase II (p-CaMK II) in the cortex, but not in the thalamus. Acute dizocilpine treatment prior to the naloxone-challenge and repeated treatment with dizocilpine alone had no effect on analgesia, withdrawal manifestations, p-CaMK II levels or c-Fos protein levels. These results showed that co-administration of dizocilpine and morphine prevented the development of morphine tolerance and dependence and suggested that the preventive effect of dizocilpine results from the regulation of c-Fos protein expression, which is possibly involved in the activation of the Ca2+/calmodulin-dependent signal cascade in the cortex." @default.
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• W1994004692 date "2004-07-01" @default.
• W1994004692 modified "2023-09-23" @default.
• W1994004692 title "Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence: an association with cortical Ca2+/calmodulin-dependent signal cascade" @default.
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• W1994004692 doi "https://doi.org/10.1016/j.bbr.2003.10.014" @default.
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