The roles of midbrain and diencephalic dopamine cell groups in the regulation of cataplexy in narcoleptic Dobermans.
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.
Okura
Mutsumi
M
Center for Narcolepsy, Stanford Sleep Center, Stanford University School of Medicine, Palo Alto, CA 94304-5485, USA.
Fujiki
Nobuhiro
N
Kita
Ichiro
I
Honda
Kazuki
K
Yoshida
Yasushi
Y
Mignot
Emmanuel
E
Nishino
Seiji
S
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*
D015259:Dopamine Agents; D004298:Dopamine