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Two kinds of mitogen‐activated protein kinase phosphatases, MKP‐1 and MKP‐3, are differentially activated by acute and chronic methamphetamine treatment in the rat brain
Author(s) -
Takaki Manabu,
Ujike Hiroshi,
Kodama Masafumi,
Takehisa Yasushi,
Nakata Kenji,
Kuroda Shigetoshi
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00615.x
Subject(s) - methamphetamine , meth , hippocampus , striatum , antagonist , sensitization , nmda receptor , neuroscience , pharmacology , medicine , dopamine , protein kinase a , endocrinology , receptor , psychology , chemistry , kinase , biochemistry , monomer , organic chemistry , acrylate , polymer
Two functionally different MAP kinase phosphatases (MKPs) were investigated to clarify their roles in behavioral sensitization to methamphetamine (METH). MKP‐1 mRNA levels increased substantially by about 60–300% in a range of brain regions, including several cortices, the striatum and thalamus 0.5–1 h after acute METH administration. After chronic METH administration its increase was less pronounced, but a more than 50% increase was still seen in the frontal cortex. MKP‐1 protein levels also increased 3 h after acute or chronic METH administration. MKP‐3 mRNA levels increased by about 30–50% in several cortices, the striatum and hippocampus 1 h after acute METH administration, but only in the hippocampus CA1 after chronic METH administration. Pre‐treatment with the D 1 dopamine receptor antagonist, SCH23390, attenuated the METH‐induced increase of MKP‐1 and MKP‐3 mRNA in every brain region, while pre‐treatment with the NMDA receptor antagonist, MK‐801, attenuated it in some regions . These findings suggest that in METH‐induced sensitization, MKP‐1 and MKP‐3 play important roles in the neural plastic modification in widespread brain regions in the earlier induction process, but in the later maintenance process, they do so only in restricted brain regions such as MKP‐1 in the frontal cortices and MKP‐3 in the hippocampus.

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