Dopamine D3 agonists into the substantia nigra aggravate cataplexy but do not modify sleep.
We have recently demonstrated that local perfusion of dopaminergic D2/D3 agonists into the ventral tegmental area (VTA) significantly aggravates cataplexy and increases sleep in narcoleptic Dobermans. We further assessed the roles of the mesostriatal dopaminergic system and found that local perfusion of quinpirole and 7-OH-DPAT into the substantia nigra (SN) significantly aggravated cataplexy, while perfusion of a D2/D3 antagonist significantly reduced cataplexy. Neither a D1 agonist nor a D1 antagonist modified cataplexy. SN perfusion of quinpirole did not significantly modify sleep, while VTA perfusion significantly increased the drowsy state. Although autoregulation of the VTA and SN dopaminergic neurons are involved in the regulation of cataplexy, both structures have distinct roles for the regulation of sleep.
Honda
K
K
Center for Narcolepsy, Department of Psychiatry and Behavioral Science, Stanford University, School of Medicine, Palo Alto, CA 94304, USA.
Riehl
J
J
Mignot
E
E
Nishino
S
S
D000818:Animals; D002385:Cataplexy / Q000139:chemically induced*; D004285:Dogs; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D019257:Quinpirole / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D050637:Receptors, Dopamine D3; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; C031349:7-hydroxy-2-N,N-dipropylaminotetralin