title: Striatal muscarinic receptor antagonism reduces 24-h food intake in association with decreased preproenkephalin gene expression.
abstract: Cholinergic interneurons of the striatum respond to motivationally relevant stimuli and are involved in appetitive learning. However, there has been relatively little inquiry into the role of striatal acetylcholine in food motivation. Here we show in rats that a single infusion of the muscarinic receptor antagonist scopolamine (0, 5.0 or 10.0 microg/0.5 microL bilaterally) potently reduced 24-h food intake following injections into either the ventral or dorsal striatum, without affecting water intake. Furthermore, muscarinic receptor blockade induced reliable and widespread reductions in striatal preproenkephalin, but not preprodynorphin, mRNA expression. These data suggest a novel role for striatal acetylcholine in modulating feeding behavior via its effects on enkephalin gene expression. As prior research indicates a critical role for striatal enkephalin in consummatory behaviors and palatability, we hypothesize that cholinergic interneurons assist in translating hypothalamic energy state signals into food-directed behaviors via their regulation of striatal opioid peptides.
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, USA. wepratt@wisc.edu
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Pratt
authors.forename: Ann E
authors.initials: AE
authors.lastname: Kelley
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology*; D013997:Time Factors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D004745:Enkephalins; D018727:Muscarinic Antagonists; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; C033660:preproenkephalin; D012601:Scopolamine