Spontaneous REM sleep is modulated by the activation of the pedunculopontine tegmental GABAB receptors in the freely moving rat.
Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify the role of GABA and its receptors in the regulation of REM sleep. To achieve this aim, specific receptors were activated differentially by local microinjection of selective GABA receptor agonists into the PPT while quantifying its effects on REM sleep in freely moving chronically instrumented rats (n = 21). The results demonstrated that when GABAB receptors were activated by local microinjection of a GABAB receptor selective agonist, baclofen, spontaneous REM sleep was suppressed in a dose-dependent manner. The optimum dose for REM sleep reduction was 1.5 nmol. In contrast, when GABAA and GABAC receptors were activated by microinjecting their receptor selective agonists, isoguvacine (ISGV) and cis-4-aminocrotonic acid (CACA), respectively, the total percentages of REM sleep did not change compared with the control values. In another eight freely moving rats, effects of baclofen application was tested on firing rates of REM-on cells (n = 12). Of those 12 neurons, 11 stopped firing immediately after application of baclofen [latency: 50 +/- 14 s (SD)] and remained almost silent for 130 +/- 12 min. Findings of the present study provide direct evidence that the PPT GABAB receptors and REM-on cells are involved in the regulation of REM sleep.
Ulloor
Jagadish
J
Sleep Research Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Mavanji
Vijayakumar
V
Saha
Subhash
S
Siwek
Donald F
DF
Datta
Subimal
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D004585:Electrooculography / Q000379:methods; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
D018682:GABA Agents; D018080:Receptors, GABA-B