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Sleep. 2010 Oct;33(10):1295-304.

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

Author information

1
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

Abstract

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.

PMID:
21061851
PMCID:
PMC2941415
DOI:
10.1093/sleep/33.10.1295
[Indexed for MEDLINE]
Free PMC Article

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