MESOPONTINE ORGANIZATION OF CHOLINERGIC AND CATECHOLAMINERGIC CELL GROUPS IN THE NORMAL AND NARCOLEPTIC DOG

Canine narcolepsy is a unique experimental model of a human sleep diso rder characterized by excessive daytime sleepiness and cataplexy. Ther e is a consensus recognition of an imbalance between cholinergic and c atecholaminergic systems in narcolepsy although the underlying mechani sms remain poorly understood. Possible substrates could be an abnormal organization, numbers and/or ratio of cholinergic to catecholaminergi c cells in the brain of narcoleptic dogs. Therefore, we sought to char acterize the corresponding neuronal populations in normal and narcolep tic dogs (Doberman Pinscher) by using choline acetyltransferase (ChAT) , nicotinamide adenosine dinucleotide phosphate (NADPH)-diaphorase, ty rosine hydroxylase (TH), and dopamine beta-hydroxylase (DBH). Choliner gic cell groups were found in an area extending from the central to th e gigantocellular tegmental field and the periventricular gray corresp onding to the pedunculopontine tegmental nucleus (PPT), the laterodors al tegmental nucleus (LDT), and the parabrachial nucleus. An almost pe rfect co-localization of ChAT and NADPH-diaphorase was also observed. Catecholaminergic cell groups detected included the ventral tegmental area, the substantia nigra, and the locus coeruleus nucleus (LC). The anatomical distribution of catecholaminergic neurons was unusual in th e dog in two important aspects: i) TH- and/or DBH-immunoreactive neuro ns of the LC were found almost exclusively in the reticular formation and not within the periventricular gray, ii) very few, if any TH-posit ive neurons were found in the central gray and dorsal raphe. Quantitat ive analysis did not reveal any significant differences in the organiz ation and the number of cells identified in the LDT, PPT, and LC of no rmal and narcoleptic dogs. Moreover, the cholinergic to catecholaminer gic ratio was found identical in the two groups. In conclusion, the pr esent results do not support the hypothesis that the neurochemical imb alance in narcolepsy could result from abnormal organization, numbers, or ratio of the corresponding neuronal populations. (C) 1997 Wiley-Li ss, Inc.