Neuropharmacological Characterization of Basal Forebrain Cholinergic Stimulated Cataplexy in Narcoleptic Canines
pp. 89-104 (doi:10.1006/exnr.1998.6787) 
Malcolm S. Reid* Seiji Nishino Mehdi Tafti Jerome M. Siegel William C. Dement Emmanuel Mignot 

Center for Narcolepsy Research, Department of Psychiatry and Behavioral Sciences, Stanford University, 1201 Welch Road/MSLS Building, Palo Alto, California, 94304-5485
*New York Veteran's Affairs Medical Center, Mail Code 116A, 423 W. 23rd Street, New York, New York, 1010
Department of Psychiatry, Neurobiology Research 151A3, University of California, Los Angeles, Sepulveda, California, 91343
Medline Abstract
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(Received September 15, 1997; accepted January 15, 1998)

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 (10-5-10-3M), but not McN-A-343 or nicotine (10-4-10-3M), produced a dose-dependent increase in cataplexy. In addition, N-methyl-D-aspartate (10-4-10-3M) and kainic acid (10-5-10-4M) did not have any effects, while muscimol (10-3M) produced a weak (P<0.10) increase in cataplexy. In control canines, carbachol (10-5-10-3M), but not oxotremorine (10-4-10-3M), produced muscle atonia after the highest concentration in one of three animals. Carbachol (10-3M)-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. Copyright 1998 Academic Press.

Key Words:   narcolepsy; cataplexy; carbachol; acetylcholine; basal forebrain.


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