Knockdown of the transcript of ERK in the brain modulates hypothalamic neuropeptide-mediated appetite control in amphetamine-treated rats.

Abstract

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 MC3 receptors were examined and compared.

KEY RESULTS:

Following amphetamine treatment, food intake, body weight and NPY expression decreased, whereas the expression of pERK, pCREB, MC3 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 MC3 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.

• Authors: Ching-Han Yu, Yih-Shou Hsieh, Pei-Ni Chen, Jeng-Rung Chen, Dong-Yih Kuo
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 175 Issue 4 Pg. 726-739 (02 2018) ISSN: 1476-5381 [Electronic] England
• PMID: 29215157 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The British Pharmacological Society.

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Neuropeptide Y
• Receptors, Neuropeptide Y
• Pro-Opiomelanocortin
• Amphetamine

Topics

• Amphetamine (pharmacology)
• Animals
• Appetite Regulation (drug effects, physiology)
• Cyclic AMP Response Element-Binding Protein (genetics, metabolism)
• Eating (drug effects, physiology)
• Feeding Behavior (drug effects, physiology)
• Gene Knockdown Techniques (methods)
• Hypothalamus (drug effects, metabolism)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Neuropeptide Y (antagonists & inhibitors, genetics, metabolism)
• Pro-Opiomelanocortin (genetics, metabolism)
• Rats
• Rats, Wistar
• Receptors, Neuropeptide Y (antagonists & inhibitors, genetics, metabolism)