Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats.
Although amphetamine (AMPH)-induced appetite suppression has been attributed to its inhibitory action on neuropeptide Y (NPY), an appetite neurotransmitter abundant in the brain, molecular mechanisms underlying this effect are not well known. This study examined the possible role of protein kinase A (PKA) and cAMP response element-binding protein (CREB) signaling in this anorectic effect, and the results showed that both PKA and CREB mRNA levels in hypothalamus were increased following AMPH treatment, which was relevant to a reduction of NPY mRNA level. To determine whether PKA or CREB was involved in the anorectic response, intracerebroventricular infusions of antisense oligonucleotide (or missense control) were performed 60 min before daily AMPH treatment in conscious rats, and results showed that either PKA or CREB knockdown could block AMPH-induced anorexia as well as restore NPY mRNA level, indicating the respective involvement of PKA and CREB signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA and CREB signaling may involve the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.
Hsieh
Yih-Shou
YS
Dept. of Physiology, Chung Shan Medical University, Taichung City 40201, Taiwan.
Yang
Shun-Fa
SF
Kuo
Dong-Yih
DY
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism; D001067:Appetite Depressants / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009068:Movement; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D001067:Appetite Depressants; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D000661:Amphetamine; D017868:Cyclic AMP-Dependent Protein Kinases