Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Amphetamine-Related Disorders / metabolism
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Animals
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Autoradiography
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Behavior, Animal / drug effects
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Benzazepines / pharmacology
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Brain / drug effects*
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Brain / enzymology*
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Cell Cycle Proteins*
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Central Nervous System Stimulants / pharmacology*
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Chronic Disease
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Dizocilpine Maleate / pharmacology
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Dopamine Antagonists / pharmacology
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Dual Specificity Phosphatase 1
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Dual Specificity Phosphatase 6
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Enzyme Activation / drug effects
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Excitatory Amino Acid Antagonists / pharmacology
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Gene Expression Regulation, Enzymologic / drug effects
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Immediate-Early Proteins / genetics
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Immediate-Early Proteins / metabolism*
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Male
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Methamphetamine / pharmacology*
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Mitogen-Activated Protein Kinases / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Phosphoprotein Phosphatases*
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Protein Phosphatase 1
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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RNA, Messenger / analysis
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Rats
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Rats, Sprague-Dawley
Substances
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Benzazepines
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Cell Cycle Proteins
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Central Nervous System Stimulants
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Dopamine Antagonists
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Excitatory Amino Acid Antagonists
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Immediate-Early Proteins
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RNA, Messenger
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Methamphetamine
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Dizocilpine Maleate
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Mitogen-Activated Protein Kinases
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Phosphoprotein Phosphatases
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Protein Phosphatase 1
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Dual Specificity Phosphatase 1
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Dual Specificity Phosphatase 6
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Dusp1 protein, rat
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Dusp6 protein, rat
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Protein Tyrosine Phosphatases