title: The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans.
abstract: Cataplexy, an emotion-triggered sudden loss of muscle tone specific to narcolepsy, is tightly associated with hypocretin deficiency. Using hypocretin receptor 2 gene (hcrtr 2)-mutated narcoleptic Dobermans, we have previously demonstrated that altered dopamine (DA) D(2/3) receptor mechanisms in mesencephalic DA nuclei are important for the induction of cataplexy. In the current study, we also found that the administration of D(2/3) agonists into diencephalic dopaminergic cell groups, including the area dorsal to the ventral tegmental area (DRVTA) and the periventricular gray (PVG) matter of the caudal thalamus (corresponding to area A11), significantly aggravated cataplexy in hcrtr 2-mutated narcoleptic Dobermans. A D(1) agonist and antagonist and a DA uptake inhibitor perfused into the DRVTA had no effect on cataplexy, suggesting an involvement of D(2/3) receptors located on DA cell bodies (i.e., autoreceptors) for the regulation of cataplexy. Because the A11 cell group projects to the spinal ventral horn, the A11 D(2/3) receptive mechanisms may directly modulate the activity of spinal motoneurons and modulate cataplexy.
authors.affiliation: Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, CA 94304-5485, USA.
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Okura
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujiki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kita
authors.forename: Kazuki
authors.initials: K
authors.lastname: Honda
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.forename: Seiji
authors.initials: S
authors.lastname: Nishino
mesh_terms: D000818:Animals; D002385:Cataplexy / Q000235:genetics / Q000378:metabolism; D004027:Diencephalon / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000502:physiology*; D009290:Narcolepsy / Q000235:genetics / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D004298:Dopamine