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

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.

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.

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.

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.