Abstract
It has been reported that neuropeptide Y (NPY) contributes to the behavioral response of amphetamine (AMPH), a psychostimulant. The present study examined whether protein kinase C (PKC)-λ signaling was involved in this action. Moreover, possible roles of glutathione peroxidase (GP) and melanocortin receptor 4 (MC4R) were also examined. Rats were given AMPH daily for 4 days. Hypothalamic NPY, PKCλ, GP and MC4R were determined and compared. Pretreatment with α-methyl-para-tyrosine could block AMPH-induced anorexia, revealing that endogenous catecholamine was involved in regulating AMPH anorexia. PKCλ, GP and MC4R were increased with maximal response on Day 2 during AMPH treatment, which were concomitant with the decreases in NPY. cAMP response element binding protein (CREB) DNA binding activity was increased during AMPH treatment, revealing the involvement of CREB-dependent gene transcription. An interruption of cerebral PKCλ transcript could partly block AMPH-induced anorexia and partly reverse NPY, MC4R and GP mRNA levels to normal. These results suggest that PKCλ participates in regulating AMPH-induced anorexia via a modulation of hypothalamic NPY gene expression and that increases of GP and MC4R may contribute to this modulation. Our results provided molecular evidence for the regulation of AMPH-induced behavioral response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amphetamine / pharmacology*
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Animals
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Anorexia / chemically induced
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Anorexia / enzymology
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Anorexia / genetics
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Antisense Elements (Genetics) / administration & dosage
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Appetite Depressants / pharmacology*
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Behavior, Animal / drug effects
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Binding Sites
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Catecholamines / metabolism
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Central Nervous System Stimulants / pharmacology*
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Cyclic AMP Response Element-Binding Protein / metabolism
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Dose-Response Relationship, Drug
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Eating / drug effects
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation
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Gene Knockdown Techniques
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Glutathione Peroxidase / genetics
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Glutathione Peroxidase / metabolism*
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Hypothalamus / drug effects*
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Hypothalamus / enzymology
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Injections, Intraventricular
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Isoenzymes / deficiency*
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Isoenzymes / genetics
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Male
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Neuropeptide Y / genetics
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Neuropeptide Y / metabolism*
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Protein Kinase C / deficiency*
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Protein Kinase C / genetics
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RNA, Messenger / metabolism
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Rats
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Rats, Wistar
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Receptor, Melanocortin, Type 4 / genetics
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Receptor, Melanocortin, Type 4 / metabolism*
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Time Factors
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Tyrosine 3-Monooxygenase / antagonists & inhibitors
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Tyrosine 3-Monooxygenase / metabolism
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alpha-Methyltyrosine / pharmacology
Substances
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Antisense Elements (Genetics)
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Appetite Depressants
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Creb1 protein, rat
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Catecholamines
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Central Nervous System Stimulants
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Isoenzymes
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Neuropeptide Y
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RNA, Messenger
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Receptor, Melanocortin, Type 4
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alpha-Methyltyrosine
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Amphetamine
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Glutathione Peroxidase
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Tyrosine 3-Monooxygenase
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Protein Kinase C
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protein kinase C lambda