New Developments in Drug Dependence Studies. Mechanisms of morphine-induced rewarding effect. Involvement of NMDA receptor subunits.

NARITA Minoru, AOKI Takeshi, SUZUKI Tsutomu

doi:10.1254/fpj.117.13

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Other Title

薬物依存研究の新展開　　モルヒネ依存およびその報酬効果の形成機序　　ＮＭＤＡ受容体サブユニットの関与
モルヒネ依存およびその報酬効果の形成機序--NMDA受容体サブユニットの関与
モルヒネイゾンオヨビソノホウシュウコウカノケイセイキジョ NMDA ジュヨウタイサブユニットノカンヨ
involvement of NMDA receptor subunits
—NMDA受容体サブユニットの関与—

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The glutamate receptor contributes to excitatory synaptic transmission in the central nervous system and plays an important role in memory acquisition, learning and neurological disorders. Molecular cloning studies have revealed that NMDA receptors consist of two families, the NR1 and NR2A-NR2D subunits, and NMDA receptors are thought to be pentameric or tetrameric complexes of the NR1 subunit with one or more of the NR2 subunits. It has been proposed that NMDA receptors are implicated in the development of opioid dependence. The non-selective NMDA receptor antagonist dizocilpine has been shown to suppress not only physical but also psychological dependence produced by morphine. An intracerebroventricular (i.c.v.) treatment with a specific antibody against the carboxyl-terminal region of the NR2B subunit abolishes the morphine-induced place preference, whereas antibodies against the NR1 and NR2A subunits do not affect the rewarding effect of morphine, indicating that the blockade of the NR2B subunit suppresses the development of the morphine-induced rewarding effect. Under these conditions, the NR2B subunit protein is up-regulated in the limbic forebrain of morphine-conditioned mice. These findings suggest that the NMDA receptor, especially NR2B subunit, is an important modulator of the development and/or expression of psychological dependence on morphine.

Journal

Folia Pharmacologica Japonica

Folia Pharmacologica Japonica 117 (1), 13-19, 2001

The Japanese Pharmacological Society

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