title: Neuropharmacological characterization of basal forebrain cholinergic stimulated cataplexy in narcoleptic canines.
abstract: Basal forebrain (BF) cholinergic regulation of cataplexy was investigated in narcoleptic canines. Specific cholinergic agonists and antagonists, and excitatory or inhibitory amino acid neurotransmitter receptor agonists, were perfused through microdialysis probes implanted bilaterally in the BF of narcoleptic canines. Cataplexy was monitored using the food-elicited cataplexy test (FECT) and recordings of electroencephalogram, electrooculogram, and electromyogram. In narcoleptic canines, carbachol and oxotremorine (10(-5)-10(-3) M), but not McN-A-343 or nicotine (10(-4)-10(-3) M), produced a dose-dependent increase in cataplexy. In addition, N-methyl-d-aspartate (10(-4)-10(-3) M) and kainic acid (10(-5)-10(-4) M) did not have any effects, while muscimol (10(-3) M) produced a weak (P < 0.10) increase in cataplexy. In control canines, carbachol (10(-5)-10(-3) M), but not oxotremorine (10(-4)-10(-3) M), produced muscle atonia after the highest concentration in one of three animals. Carbachol (10(-3) M)-induced cataplexy in narcoleptic canines was blocked by equimolar perfusion with the muscarinic antagonists atropine, gallamine, and 4-DAMP but not pirenzepine. These findings indicate that carbachol-stimulated cataplexy in the BF of narcoleptic canines is mediated by M2, and perhaps M3, muscarinic receptors. The release of acetylcholine in the BF was also examined during FECT and non-FECT behavioral stimulation in narcoleptic and control canines. A significant increase in acetylcholine release was found in both narcoleptic and control BF during FECT stimulation. In contrast, simple motor activity and feeding, approximating that which occurs during an FECT, did not affect acetylcholine release in the BF of narcoleptic canines. These findings indicate that BF acetylcholine release is enhanced during learned emotion/reward associated behaviors in canines.
authors.affiliation: Center for Narcolepsy Research, Department of Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Road/MSLS Building, Palo Alto, California, 94304-5485, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Reid
authors.forename: S
authors.initials: S
authors.lastname: Nishino
authors.forename: M
authors.initials: M
authors.lastname: Tafti
authors.forename: J M
authors.initials: JM
authors.lastname: Siegel
authors.forename: W C
authors.initials: WC
authors.lastname: Dement
authors.forename: E
authors.initials: E
authors.lastname: Mignot
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D002385:Cataplexy / Q000188:drug therapy* / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D016548:Prosencephalon / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
chemical_list: D018755:GABA Agonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010880:Piperidines; D009118:Muscimol; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D009538:Nicotine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D000109:Acetylcholine; D005703:Gallamine Triethiodide