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Knockdown of the transcript of ERK in the brain modulates hypothalamic neuropeptide‐mediated appetite control in amphetamine‐treated rats
Author(s) -
Yu ChingHan,
Hsieh YihShou,
Chen PeiNi,
Chen JengRung,
Kuo DongYih
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14120
Subject(s) - creb , endocrinology , medicine , neuropeptide y receptor , amphetamine , appetite , hypothalamus , dopamine , mapk/erk pathway , melanocortin , proopiomelanocortin , neuropeptide , receptor , chemistry , signal transduction , transcription factor , biochemistry , gene
Background and Purpose Amphetamine is a releaser of dopamine stored in synaptic terminals, which can suppress appetite by changing the expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the hypothalamus. This study explored whether ERKs are involved in appetite control mediated by cAMP response element binding protein (CREB), NPY and POMC in amphetamine‐treated rats. Experimental Approach Rats were given amphetamine for 4 days, and changes in feeding behaviour and expression levels of phosphorylated‐ERK (pERK), pCREB, NPY and melanocortin MC 3 receptors were examined and compared. Key Results Following amphetamine treatment, food intake, body weight and NPY expression decreased, whereas the expression of pERK, pCREB, MC 3 receptors and pCREB/DNA binding activity increased. In amphetamine‐treated rats, both cerebral ERK knockdown and pretreatment with a peripheral dopamine receptor antagonist decreased NPY but increased pERK, pCREB and MC 3 receptor expression. Moreover, the immunofluorescence of hypothalamic pERK increased following amphetamine treatment. Conclusions and Implications These results suggest that ERK/CREB signalling participates in the effects mediated by dopamine receptor/NPY/POMC on appetite control in rats treated with amphetamine. These findings advance the knowledge on the involvement of ERK/CREB signalling in the reciprocal regulation by NPY and POMC of appetite after amphetamine treatment.