Role of noradrenergic and GABA-ergic inputs in pedunculopontine tegmentum for regulation of rapid eye movement sleep in rats

Neuropharmacology. 2006 Jul;51(1):1-11. doi: 10.1016/j.neuropharm.2006.02.006. Epub 2006 Apr 17.


Rapid eye movement (REM) sleep disturbance is associated with several psycho-behavioral disorders, hence, it is important to understand its neural mechanism of regulation. Although it was known that the noradrenergic (NA-ergic) neurons from locus coeruleus (LC) project to the pedunculopontine tegmentum (PPT), the role of noradrenaline (NA) alone and in association with GABA, an inhibitory neurotransmitter, in PPT for REM sleep regulation was not known and was investigated in this study in freely moving normally behaving rats. Rats were surgically prepared for electrophysiological sleep-wake recording and simultaneous bilateral microinjections into PPT. 200nl of prazosin (alpha1-antagonist) or clonidine (alpha2-agonist) or propranolol (beta-antagonist) or combination of picrotoxin (GABA-A antagonist) and clonidine or vehicle (control) was microinjected bilaterally into PPT using a remote-controlled pump and the effects on REM sleep compared. Prazosin, clonidine and propranolol increased the total time spent in REM sleep whereas co-injection of picrotoxin and clonidine did not affect REM sleep. The results suggest that NA in PPT tonically inhibits REM sleep, possibly by acting on the cholinergic REM-ON neurons, while GABA inhibits the release of NA for REM sleep regulation. A model of neural connections explaining such regulation has been presented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Choline O-Acetyltransferase / metabolism
  • Clonidine / administration & dosage
  • Clonidine / pharmacology
  • GABA Antagonists / administration & dosage
  • GABA Antagonists / pharmacology
  • Hippocampus / physiology
  • Immunohistochemistry
  • Male
  • Mesencephalon / physiology*
  • Microinjections
  • Norepinephrine / physiology*
  • Picrotoxin / administration & dosage
  • Picrotoxin / pharmacology
  • Polysomnography / drug effects
  • Pons / physiology*
  • Prazosin / administration & dosage
  • Prazosin / pharmacology
  • Propranolol / administration & dosage
  • Propranolol / pharmacology
  • Rats
  • Rats, Wistar
  • Sleep, REM / drug effects
  • Sleep, REM / physiology*
  • Wakefulness / drug effects
  • Wakefulness / physiology
  • gamma-Aminobutyric Acid / physiology*


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Antagonists
  • GABA Antagonists
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • Propranolol
  • Choline O-Acetyltransferase
  • Clonidine
  • Norepinephrine
  • Prazosin