Effect of K+ channel modulation on mouse feeding behaviour.
The K+ channel antagonists, glucose (100 microg per mouse i.c.v.), tetraethylammonium (1 microg per mouse i.c.v.) and apamin (1 ng per mouse i.c.v.), reduced food intake of mice comparably to the two anorectic drugs, amphetamine (10 microg per mouse i.c.v.) and cocaine (50 microg per mouse i.c.v.). Conversely, the K+ channel openers, minoxidil (5 microg per mouse i.c.v.) and pinacidil (10 microg per mouse i.c.v.), elicited an orectic effect of the same intensity as that induced by 2-deoxyglucose (200 microg per mouse i.c.v.), aurothioglucose (200 microg per mouse i.c.v.) and neuropeptide Y (0.5 microg per mouse i.c.v.). The antisense oligodeoxyribonucleotide (1-3 nmol per injection) to mKv1.1 gene produced, at 72 h, a dose-dependent increase in food intake. A quantitative reverse transcription-polymerase chain reaction (RT-PCR) study demonstrated a reduction in cerebral mRNA levels only in the antisense oligodeoxyribonucleotide-treated group, indicating the absence of a sequence-independent action. Mice receiving the K+ channel modulators or antisense oligodeoxyribonucleotide had unmodified motor coordination and inspection activity as revealed, respectively, by the rotarod and hole-board tests. The integrity and functionality of central K+ channels appears, therefore, to be fundamental in the regulation of food intake by mice.
Ghelardini
C
C
Department of Pharmacology, University of Florence, Italy. bartolin@stat.ds.unifi.it
Galeotti
N
N
Pecori Vettori
A
A
Capaccioli
S
S
Quattrone
A
A
Bartolini
A
A
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008914:Minoxidil / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D020110:Pinacidil; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000819:agonists / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000008:administration & dosage / Q000494:pharmacology
D006146:Guanidines; D016376:Oligonucleotides, Antisense; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D001030:Apamin; D008914:Minoxidil; D019789:Tetraethylammonium; D020110:Pinacidil; D000661:Amphetamine; D003042:Cocaine; D005947:Glucose