Spontaneous REM Sleep Is Modulated By the Activation of the Pedunculopontine Tegmental GABAB Receptors in the Freely Moving Rat

• Published in: Journal of neurophysiology 2004-04, Vol.91 (4), p.1822-1831
• Main Authors: Ulloor, Jagadish, Mavanji, Vijayakumar, Saha, Subhash, Siwek, Donald F, Datta, Subimal
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Dose-Response Relationship, Drug; Electroencephalography - methods; Electromyography - methods; Electrooculography - methods; GABA Agents - pharmacology; Male; Microinjections - methods; Pedunculopontine Tegmental Nucleus - cytology; Pedunculopontine Tegmental Nucleus - drug effects; Pedunculopontine Tegmental Nucleus - physiology; Rats; Rats, Sprague-Dawley; Receptors, GABA-B - drug effects; Receptors, GABA-B - physiology; Sleep, REM - drug effects; Sleep, REM - physiology; Time Factors; Wakefulness - drug effects; Wakefulness - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01104.2003

Sleep Research Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118 Submitted 14 November 2003; accepted in final form 16 December 2003 Considerable evidence suggests that the neurotransmitter -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 GABA B receptors were activated by local microinjection of a GABA B 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 GABA A and GABA C 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 GABA B receptors and REM- ON cells are involved in the regulation of REM sleep. Address for reprint requests and other correspondence: S. Datta, Sleep Research Laboratory, Dept. of Psychiatry, Boston University School of Medicine, M 902, 715 Albany St., Boston, MA 02118 (E-mail: SUBIMAL{at}BU.EDU ).