Involvement of cyclic AMP systems in morphine physical dependence in mice

Prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor

Takayoshi Mamiya, Yukihiro Noda, Xiuhai Ren, Moustafa Hamdy, Shoei Furukawa, Tsutomu Kameyama, Kiyofumi Yamada, Toshitaka Nabeshima

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

1. In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. 2. Mice, which received morphine (10 mg kg-1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg-1 i.p.) on the 6th day. 3. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg-1 i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. 4. In naïve mice, acute morphine treatment (10 mg kg-1 s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg-1 i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. 5. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

Original languageEnglish
Pages (from-to)1111-1117
Number of pages7
JournalBritish Journal of Pharmacology
Volume132
Issue number5
DOIs
Publication statusPublished - 01-01-2001
Externally publishedYes

Fingerprint

Phosphodiesterase 4 Inhibitors
Morphine Dependence
Rolipram
Cyclic AMP
Morphine
Naloxone
Thalamus
Phosphodiesterase Inhibitors
Tremor
Cerebral Cortex

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Mamiya, Takayoshi ; Noda, Yukihiro ; Ren, Xiuhai ; Hamdy, Moustafa ; Furukawa, Shoei ; Kameyama, Tsutomu ; Yamada, Kiyofumi ; Nabeshima, Toshitaka. / Involvement of cyclic AMP systems in morphine physical dependence in mice : Prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor. In: British Journal of Pharmacology. 2001 ; Vol. 132, No. 5. pp. 1111-1117.
@article{caec5e9d99234036b0ab65c6ca0dc557,
title = "Involvement of cyclic AMP systems in morphine physical dependence in mice: Prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor",
abstract = "1. In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. 2. Mice, which received morphine (10 mg kg-1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg-1 i.p.) on the 6th day. 3. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg-1 i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. 4. In na{\"i}ve mice, acute morphine treatment (10 mg kg-1 s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg-1 i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. 5. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.",
author = "Takayoshi Mamiya and Yukihiro Noda and Xiuhai Ren and Moustafa Hamdy and Shoei Furukawa and Tsutomu Kameyama and Kiyofumi Yamada and Toshitaka Nabeshima",
year = "2001",
month = "1",
day = "1",
doi = "10.1038/sj.bjp.0703912",
language = "English",
volume = "132",
pages = "1111--1117",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "5",

}

Involvement of cyclic AMP systems in morphine physical dependence in mice : Prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor. / Mamiya, Takayoshi; Noda, Yukihiro; Ren, Xiuhai; Hamdy, Moustafa; Furukawa, Shoei; Kameyama, Tsutomu; Yamada, Kiyofumi; Nabeshima, Toshitaka.

In: British Journal of Pharmacology, Vol. 132, No. 5, 01.01.2001, p. 1111-1117.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Involvement of cyclic AMP systems in morphine physical dependence in mice

T2 - Prevention of development of morphine dependence by rolipram, a phosphodiesterase 4 inhibitor

AU - Mamiya, Takayoshi

AU - Noda, Yukihiro

AU - Ren, Xiuhai

AU - Hamdy, Moustafa

AU - Furukawa, Shoei

AU - Kameyama, Tsutomu

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 1. In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. 2. Mice, which received morphine (10 mg kg-1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg-1 i.p.) on the 6th day. 3. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg-1 i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. 4. In naïve mice, acute morphine treatment (10 mg kg-1 s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg-1 i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. 5. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

AB - 1. In this study, we examined whether morphine dependence was inhibited by rolipram, a cyclic AMP selective phosphodiesterase inhibitor in mice, since a role for the cyclic AMP systems in the development of morphine dependence has been reported. 2. Mice, which received morphine (10 mg kg-1 s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing and forepaw tremor following naloxone challenge (5 mg kg-1 i.p.) on the 6th day. 3. Such mice exhibited a significant elevation of cyclic AMP levels in the thalamus compared to control mice. However, co-administration of rolipram (1 mg kg-1 i.p.) with morphine for 5 days significantly attenuated the severity of the withdrawal syndrome and the increase in the cyclic AMP levels after the administration of naloxone. 4. In naïve mice, acute morphine treatment (10 mg kg-1 s.c.) decreased cyclic AMP levels in the thalamus and cerebral cortex 10 min later. The decrease of cyclic AMP levels induced by acute morphine treatment was blocked by co-administration of rolipram (1 mg kg-1 i.p.). However, acute rolipram did not affect the naloxone-precipitated morphine withdrawal syndrome. 5. These results suggest that the elevation of the cyclic AMP levels is involved in the development of morphine withdrawal syndrome and that blockade of the morphine-induced reduction of cyclic AMP levels by chronic rolipram inhibits the development of dependence and the behavioural and biochemical changes induced by naloxone. Furthermore, rolipram may be a useful drug for attenuating the development of morphine dependence.

UR - http://www.scopus.com/inward/record.url?scp=0035081254&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035081254&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0703912

DO - 10.1038/sj.bjp.0703912

M3 - Article

VL - 132

SP - 1111

EP - 1117

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 5

ER -