Dopaminergic regulation of sleep and cataplexy in a murine model of narcolepsy

Sleep. 2010 Oct;33(10):1295-304. doi: 10.1093/sleep/33.10.1295.


Study objectives: To determine if the dopaminergic system modulates cataplexy, sleep attacks and sleep-wake behavior in narcoleptic mice.

Design: Hypocretin/orexin knockout (i.e., narcoleptic) and wild-type mice were administered amphetamine and specific dopamine receptor modulators to determine their effects on sleep, cataplexy and sleep attacks.

Patients or participants: Hypocretin knockout (n = 17) and wild-type mice (n = 21).

Interventions: Cataplexy, sleep attacks and sleep-wake behavior were identified using electroencephalogram, electromyogram and videography. These behaviors were monitored for 4 hours after an i.p. injection of saline, amphetamine and specific dopamine receptor modulators (D1- and D2-like receptor modulators).

Measurements and results: Amphetamine (2 mg/kg), which increases brain dopamine levels, decreased sleep attacks and cataplexy by 61% and 67%, suggesting that dopamine transmission modulates such behaviors. Dopamine receptor modulation also had powerful effects on sleep attacks and cataplexy. Activation (SKF 38393; 20 mg/kg) and blockade (SCH 23390; 1 mg/kg) of D1-like receptors decreased and increased sleep attacks by 77% and 88%, without affecting cataplexy. Pharmacological activation of D2-like receptors (quinpirole; 0.5 mg/kg) increased cataplectic attacks by 172% and blockade of these receptors (eticlopride; 1 mg/kg) potently suppressed them by 97%. Manipulation of D2-like receptors did not affect sleep attacks.

Conclusions: We show that the dopaminergic system plays a role in regulating both cataplexy and sleep attacks in narcoleptic mice. We found that cataplexy is modulated by a D2-like receptor mechanism, whereas dopamine modulates sleep attacks by a D1-like receptor mechanism. These results support a role for the dopamine system in regulating sleep attacks and cataplexy in a murine model of narcolepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • Amphetamine / pharmacology
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Benzazepines / pharmacology
  • Cataplexy / physiopathology*
  • Disease Models, Animal
  • Dopamine Agents / pharmacology*
  • Dopamine Agonists / pharmacology*
  • Dopamine Antagonists / pharmacology*
  • Electroencephalography / drug effects
  • Electromyography / drug effects
  • Male
  • Mice
  • Mice, Knockout
  • Narcolepsy / physiopathology
  • Quinpirole / pharmacology
  • Receptors, Dopamine / drug effects
  • Salicylamides / pharmacology
  • Sleep / drug effects*
  • Videotape Recording


  • Benzazepines
  • Dopamine Agents
  • Dopamine Agonists
  • Dopamine Antagonists
  • Receptors, Dopamine
  • SCH 23390
  • Salicylamides
  • Quinpirole
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • Amphetamine
  • eticlopride