Attenuation of the development of morphine dependence/tolerance by nefiracetam

Involvement of adenosine 3':5'-cyclic monophosphate system

Akio Itoh, Tadashi Shiotani, Shinobu Nakayama, Takayoshi Mamiya, Takaaki Hasegawa, Yukihiro Noda, Toshitaka Nabeshima

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Biochemical changes such as intracellular cAMP and Ca2+ underlying morphine dependence and tolerance have been suggested. Therefore, we investigated the effects of nefiracetam (N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl) acetamide), which increases intracellular cAMP and Ca2+ levels, on the development of morphine dependence and tolerance. Mice administered morphine (6 or 20 mg kg-1) twice daily for 5 days, showed withdrawal symptoms (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg kg-1), indicating morphine dependence. Furthermore, tolerance to the analgesic effect of morphine was observed in these mice. Co-administration of nefiracetam (5 or 10 mg kg-1) with morphine during the pretreatment period, significantly reduced the signs of withdrawal symptoms, moreover, the tolerance was significantly attenuated. Elevation of cAMP levels in the cortex was observed in morphine-dependent mice, but not in mice co-administered nefiracetam. Acute administration of nefiracetam shows no effect on the withdrawal symptoms and the analgesic effect in morphine-naive mice. Theophylline (3 or 10 mg kg-1) tended to attenuate and enprofylline (10 or 30 mg kg-1) significantly attenuated the development of morphine dependence and tolerance. These findings suggest that co-administration of nefiracetam or compounds, which increase the cAMP level, may be a useful strategy for attenuating the development of morphine dependence and tolerance in the clinic. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalBehavioural Brain Research
Volume115
Issue number1
DOIs
Publication statusPublished - 01-10-2000
Externally publishedYes

Fingerprint

Morphine Dependence
Adenosine
Morphine
Substance Withdrawal Syndrome
Analgesics
Theophylline
Naloxone
Signs and Symptoms
Weight Loss
Diarrhea
Body Weight
nefiracetam

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Itoh, Akio ; Shiotani, Tadashi ; Nakayama, Shinobu ; Mamiya, Takayoshi ; Hasegawa, Takaaki ; Noda, Yukihiro ; Nabeshima, Toshitaka. / Attenuation of the development of morphine dependence/tolerance by nefiracetam : Involvement of adenosine 3':5'-cyclic monophosphate system. In: Behavioural Brain Research. 2000 ; Vol. 115, No. 1. pp. 65-74.
@article{6c624221e46a43489e913e0c4595144e,
title = "Attenuation of the development of morphine dependence/tolerance by nefiracetam: Involvement of adenosine 3':5'-cyclic monophosphate system",
abstract = "Biochemical changes such as intracellular cAMP and Ca2+ underlying morphine dependence and tolerance have been suggested. Therefore, we investigated the effects of nefiracetam (N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl) acetamide), which increases intracellular cAMP and Ca2+ levels, on the development of morphine dependence and tolerance. Mice administered morphine (6 or 20 mg kg-1) twice daily for 5 days, showed withdrawal symptoms (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg kg-1), indicating morphine dependence. Furthermore, tolerance to the analgesic effect of morphine was observed in these mice. Co-administration of nefiracetam (5 or 10 mg kg-1) with morphine during the pretreatment period, significantly reduced the signs of withdrawal symptoms, moreover, the tolerance was significantly attenuated. Elevation of cAMP levels in the cortex was observed in morphine-dependent mice, but not in mice co-administered nefiracetam. Acute administration of nefiracetam shows no effect on the withdrawal symptoms and the analgesic effect in morphine-naive mice. Theophylline (3 or 10 mg kg-1) tended to attenuate and enprofylline (10 or 30 mg kg-1) significantly attenuated the development of morphine dependence and tolerance. These findings suggest that co-administration of nefiracetam or compounds, which increase the cAMP level, may be a useful strategy for attenuating the development of morphine dependence and tolerance in the clinic. (C) 2000 Elsevier Science B.V.",
author = "Akio Itoh and Tadashi Shiotani and Shinobu Nakayama and Takayoshi Mamiya and Takaaki Hasegawa and Yukihiro Noda and Toshitaka Nabeshima",
year = "2000",
month = "10",
day = "1",
doi = "10.1016/S0166-4328(00)00237-0",
language = "English",
volume = "115",
pages = "65--74",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",
number = "1",

}

Attenuation of the development of morphine dependence/tolerance by nefiracetam : Involvement of adenosine 3':5'-cyclic monophosphate system. / Itoh, Akio; Shiotani, Tadashi; Nakayama, Shinobu; Mamiya, Takayoshi; Hasegawa, Takaaki; Noda, Yukihiro; Nabeshima, Toshitaka.

In: Behavioural Brain Research, Vol. 115, No. 1, 01.10.2000, p. 65-74.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Attenuation of the development of morphine dependence/tolerance by nefiracetam

T2 - Involvement of adenosine 3':5'-cyclic monophosphate system

AU - Itoh, Akio

AU - Shiotani, Tadashi

AU - Nakayama, Shinobu

AU - Mamiya, Takayoshi

AU - Hasegawa, Takaaki

AU - Noda, Yukihiro

AU - Nabeshima, Toshitaka

PY - 2000/10/1

Y1 - 2000/10/1

N2 - Biochemical changes such as intracellular cAMP and Ca2+ underlying morphine dependence and tolerance have been suggested. Therefore, we investigated the effects of nefiracetam (N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl) acetamide), which increases intracellular cAMP and Ca2+ levels, on the development of morphine dependence and tolerance. Mice administered morphine (6 or 20 mg kg-1) twice daily for 5 days, showed withdrawal symptoms (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg kg-1), indicating morphine dependence. Furthermore, tolerance to the analgesic effect of morphine was observed in these mice. Co-administration of nefiracetam (5 or 10 mg kg-1) with morphine during the pretreatment period, significantly reduced the signs of withdrawal symptoms, moreover, the tolerance was significantly attenuated. Elevation of cAMP levels in the cortex was observed in morphine-dependent mice, but not in mice co-administered nefiracetam. Acute administration of nefiracetam shows no effect on the withdrawal symptoms and the analgesic effect in morphine-naive mice. Theophylline (3 or 10 mg kg-1) tended to attenuate and enprofylline (10 or 30 mg kg-1) significantly attenuated the development of morphine dependence and tolerance. These findings suggest that co-administration of nefiracetam or compounds, which increase the cAMP level, may be a useful strategy for attenuating the development of morphine dependence and tolerance in the clinic. (C) 2000 Elsevier Science B.V.

AB - Biochemical changes such as intracellular cAMP and Ca2+ underlying morphine dependence and tolerance have been suggested. Therefore, we investigated the effects of nefiracetam (N-(2,6-dimethyl-phenyl)-2(2-oxo-1-pyrrolidinyl) acetamide), which increases intracellular cAMP and Ca2+ levels, on the development of morphine dependence and tolerance. Mice administered morphine (6 or 20 mg kg-1) twice daily for 5 days, showed withdrawal symptoms (jumping, diarrhea and body weight loss) after naloxone challenge (5 mg kg-1), indicating morphine dependence. Furthermore, tolerance to the analgesic effect of morphine was observed in these mice. Co-administration of nefiracetam (5 or 10 mg kg-1) with morphine during the pretreatment period, significantly reduced the signs of withdrawal symptoms, moreover, the tolerance was significantly attenuated. Elevation of cAMP levels in the cortex was observed in morphine-dependent mice, but not in mice co-administered nefiracetam. Acute administration of nefiracetam shows no effect on the withdrawal symptoms and the analgesic effect in morphine-naive mice. Theophylline (3 or 10 mg kg-1) tended to attenuate and enprofylline (10 or 30 mg kg-1) significantly attenuated the development of morphine dependence and tolerance. These findings suggest that co-administration of nefiracetam or compounds, which increase the cAMP level, may be a useful strategy for attenuating the development of morphine dependence and tolerance in the clinic. (C) 2000 Elsevier Science B.V.

UR - http://www.scopus.com/inward/record.url?scp=0033833836&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033833836&partnerID=8YFLogxK

U2 - 10.1016/S0166-4328(00)00237-0

DO - 10.1016/S0166-4328(00)00237-0

M3 - Article

VL - 115

SP - 65

EP - 74

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

IS - 1

ER -