Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence

An association with cortical Ca 2+ /calmodulin- dependent signal cascade

Moustafa Mahmoud Hamdy, Yukihiro Noda, Masayuki Miyazaki, Takayoshi Mamiya, Ayumu Nozaki, Atsumi Nitta, Merfat Sayed, Abdel Azim Assi, Adel Gomaa, Toshitaka Nabeshima

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 Ca 2+ /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 Ca 2+ /calmodulin-dependent signal cascade in the cortex.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalBehavioural Brain Research
Volume152
Issue number2
DOIs
Publication statusPublished - 09-07-2004
Externally publishedYes

Fingerprint

Morphine Dependence
Dizocilpine Maleate
Calmodulin
Morphine
Proto-Oncogene Proteins c-fos
Naloxone
Thalamus
Calcium-Calmodulin-Dependent Protein Kinases
Phosphorylation
N-Methyl-D-Aspartate Receptors
Analgesia

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Hamdy, Moustafa Mahmoud ; Noda, Yukihiro ; Miyazaki, Masayuki ; Mamiya, Takayoshi ; Nozaki, Ayumu ; Nitta, Atsumi ; Sayed, Merfat ; Assi, Abdel Azim ; Gomaa, Adel ; Nabeshima, Toshitaka. / Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence : An association with cortical Ca 2+ /calmodulin- dependent signal cascade. In: Behavioural Brain Research. 2004 ; Vol. 152, No. 2. pp. 263-270.
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Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence : An association with cortical Ca 2+ /calmodulin- dependent signal cascade. / Hamdy, Moustafa Mahmoud; Noda, Yukihiro; Miyazaki, Masayuki; Mamiya, Takayoshi; Nozaki, Ayumu; Nitta, Atsumi; Sayed, Merfat; Assi, Abdel Azim; Gomaa, Adel; Nabeshima, Toshitaka.

In: Behavioural Brain Research, Vol. 152, No. 2, 09.07.2004, p. 263-270.

Research output: Contribution to journalArticle

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T1 - Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence

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AU - Hamdy, Moustafa Mahmoud

AU - Noda, Yukihiro

AU - Miyazaki, Masayuki

AU - Mamiya, Takayoshi

AU - Nozaki, Ayumu

AU - Nitta, Atsumi

AU - Sayed, Merfat

AU - Assi, Abdel Azim

AU - Gomaa, Adel

AU - Nabeshima, Toshitaka

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