Morphine activates Arc expression in the mouse striatum and in mouse neuroblastoma Neuro2A MOR1A cells expressing μ-opioid receptors

• Published in: Journal of neuroscience research 2005-11, Vol.82 (4), p.563-570
• Main Authors: Ziółkowska, Barbara, Urbański, Michael J., Wawrzczak-Bargieła, Agnieszka, Bilecki, Wiktor, Przewłocki, Ryszard
• Format: Article
• Language: English
• Subjects: AIDS-Related Complex - genetics; AIDS-Related Complex - metabolism; Analysis of Variance; Animals; Blotting, Western - methods; Cell Line, Tumor; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dose-Response Relationship, Drug; Drug Administration Schedule; drug dependence; Drug Interactions; Enkephalin, Ala-MePhe-Gly- - pharmacology; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; Gene Expression - drug effects; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; immediate early gene induction; Indoles - pharmacology; Male; Maleimides - pharmacology; Mice; Mice, Inbred C57BL; Morphine - administration & dosage; Narcotics - administration & dosage; Neuroblastoma - metabolism; plasticity; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Time Factors; μ-opioid receptor
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.20661

Activity‐regulated cytoskeleton‐associated protein (Arc) is an effector immediate early gene product implicated in long‐term potentiation and other forms of neuroplasticity. Earlier studies demonstrated Arc induction in discrete brain regions by several psychoactive substances, including drugs of abuse. In the present experiments, the influence of morphine on Arc expression was assessed by quantitative reverse transcription real‐time PCR and Western blotting in vivo in the mouse striatum/nucleus accumbens and, in vitro, in the mouse Neuro2A MOR1A cell line, expressing μ‐opioid receptor. An acute administration of morphine produced a marked increase in Arc mRNA and protein level in the mouse striatum/nucleus accumbens complex. After prolonged opiate treatment, tolerance to the stimulatory effect of morphine on Arc expression developed. No changes in the striatal Arc mRNA levels were observed during spontaneous or opioid antagonist‐precipitated morphine withdrawal. In Neuro2A MOR1A cells, acute, but not prolonged, morphine treatment elevated Arc mRNA level by activation of μ‐opioid receptor. This was accompanied by a corresponding increase in Arc protein level. Inhibition experiments revealed that morphine induced Arc expression in Neuro2A MOR1A cells via intracellular signaling pathways involving mitogen‐activated protein (MAP) kinases and protein kinase C. These results lend further support to the notion that stimulation of opioid receptors may exert an activating influence on some intracellular pathways and leads to induction of immediate early genes. They also demonstrate that Arc is induced in the brain in vivo after morphine administration and thus may play a role in neuroadaptations produced by the drug. © 2005 Wiley‐Liss, Inc.