Molecular pharmacological study on he roles of brain cytokines in narcotic dependence

脑细胞因子在麻醉依赖中作用的分子药理学研究

• 批准号: 07457538
• 负责人: SATOH Masamichi
• 金额: $ 4.86万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457538/
• 关键词: morphine; narcotics; dependence; cytokines; interleukins; microglia; neuro-immune interaction; インターロイキン

Intracisternal injection of interleukin-1beta was shown to suppress naloxone-precipitated with-drawal syndrome in morphine dependent mouse. This effect of interleukin-1beta was mediated by CRF and prostaglandin E2. In order to clarify the target cells for interleukin-1beta in the brain, we visualized the cells expressing type 1 and type 2 interleukin-1 receptors using an in situ hybridization technique. In morphine-dependent mouse, prostaglandin E2 suppressed the withdrawal syndrome through EP3 receptors. Prostaglandin EP3 agonists suppressed the withdrawal syndrome also in the morphine-dependent rats, and attenuated the experssion of c-fos mRNA in various brain regions including the locus ceruleus. Double in situ hybridization study revealed that most of the tyrosine hydroxylase mRNA-positive neurons in the locus ceruleus expressed mu-opioid receptor mRNA and more than half of those neurons were positive to EP3 receptor mRNA,indicating that an EP3 agonist acts on the locus ceruleus noradrenergic neurons expressing mu-opioid receptors. EP3 agonists possibly suppress the excitation of the locus ceruleus noradrenergic neurons to inhibit the morphine withdrawal syndrome precipitated by naloxone.

脑池内注射白细胞介素-1 β可抑制吗啡依赖小鼠纳洛酮催促戒断综合征。白细胞介素-1 β的这种作用由CRF和前列腺素E2介导。为了阐明白细胞介素-1 β在脑中的靶细胞，我们使用原位杂交技术观察表达1型和2型白细胞介素-1受体的细胞。前列腺素E2通过EP 3受体抑制吗啡依赖小鼠戒断症状。前列腺素EP 3激动剂也抑制吗啡依赖大鼠的戒断综合征，并减弱包括蓝斑在内的各个脑区c-fos mRNA的表达。双重原位杂交结果显示，蓝斑内酪氨酸羟化酶mRNA阳性神经元大多表达μ阿片受体mRNA，半数以上表达EP 3受体mRNA，表明EP 3激动剂作用于表达μ阿片受体的蓝斑去甲肾上腺素能神经元。EP 3激动剂可能通过抑制蓝斑去甲肾上腺素能神经元的兴奋来抑制纳洛酮诱发的吗啡戒断综合征。

项目成果

Katsumata. S.: "Intracisternal administration of interleukin-1β attenuates naloxone-precipitated withdrawal in morphine-dependent mice." Eur. J. Pharmacol.278. 143-150 (1995)

Katsumata.：“脑室内注射白细胞介素-1β 可减轻吗啡依赖性小鼠的戒断反应。”Eur. J. Pharmacol.278（1995）。

Yamakuni, H.: "Localization of the mRNA for leukemia inhibitory factor receptor in the rat brain." J. Neuroimmun.70. 45-53 (1996)

Yamakuni, H.：“白血病抑制因子受体 mRNA 在大鼠大脑中的定位。”

Yabuuchi, K.: "Induction of interleukin-1β mRNA in the hypothalamus following subcutaneous injections of formalin into the rat hind paws." Neurosci. Lett.207. 109-112 (1996)

Yabuuchi, K.：“向大鼠后爪皮下注射白细胞介素 1β mRNA”，《Neurosci》207. 109-112 (1996)。

Nakagawa, T.: "Suppression of naloxone-precipitated withdrawal jumps in morphine-dependent mice by stimulation of prostaglandin EP_3 receptor." Br. J. Pharmacol.116. 2661-2666 (1995)

Nakakawa, T.：“通过刺激前列腺素 EP_3 受体来抑制吗啡依赖小鼠中纳洛酮引发的戒断跳跃。”

Katsumata.S.: "Intracisternal administration of interleukin-1beta attenuates naloxone-precipitated withdrawal in morphine-dependent mice" Eur.J.Pharmacol.278. 143-150 (1995)

Katsumata.S.：“脑室内给予白细胞介素-1β 可减轻吗啡依赖性小鼠中纳洛酮引发的戒断”Eur.J.Pharmacol.278。