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ABSTRACT: Background and purpose
Appetite suppression induced by amphetamine has been attributed to its inhibition of neuropeptide Y (NPY) neurons and activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus. This study examined whether STAT3 was involved in these actions of amphetamine.Experimental approach
Rats were given amphetamine daily for 4 days. Changes in the expression of NPY, POMC, melanocortin MC3 receptors, PI3K and STAT3 in the hypothalamus were assessed by RT-PCR and Western blotting. Antisense oligonucleotides to STAT3 were also used.Key results
Expression of NPY decreased with a maximum effect day 2 of amphetamine treatment. Expression of POMC, MC3 receptors, PI3K and STAT3 increased with a maximum response on day 2. Moreover, phosphorylation of STAT3 and its DNA binding activity increased and was expressed in a similar pattern. Infusion (i.c.v.) of STAT3 antisense at 60 min before amphetamine treatment, partly blocked amphetamine-induced anorexia and modulated expression of NPY, POMC, MC3 receptors and PI3K, indicating the involvement of STAT3 in amphetamine-treated rats.Conclusions and implications
Hypothalamic PI3K-STAT3 signalling participated in the regulation of NPY- and POMC-mediated appetite suppression. These findings may contribute to a better understanding of anorectic drugs.
SUBMITTER: Chu SC
PROVIDER: S-EPMC4080976 | biostudies-literature | 2014 Jul
REPOSITORIES: biostudies-literature
Chu Shu-Chen SC Chen Pei-Ni PN Hsieh Yih-Shou YS Yu Ching-Han CH Lin Meng-Hsuan MH Lin Yan-Han YH Kuo Dong-Yih DY
British journal of pharmacology 20140701 13
<h4>Background and purpose</h4>Appetite suppression induced by amphetamine has been attributed to its inhibition of neuropeptide Y (NPY) neurons and activation of pro-opiomelanocortin (POMC) neurons in the hypothalamus. This study examined whether STAT3 was involved in these actions of amphetamine.<h4>Experimental approach</h4>Rats were given amphetamine daily for 4 days. Changes in the expression of NPY, POMC, melanocortin MC3 receptors, PI3K and STAT3 in the hypothalamus were assessed by RT-PC ...[more]