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1 Psychiatry, Boston University School of Medicine, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: SUBIMAL{at}BU.EDU.
Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brainstem are critically involved in the regulation of 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 to the control values. In another 8 freely moving rats, effects of Baclofen application was tested on firing rates of REM-on cells (n=12). Of those 12 neurons, eleven stopped firing immediately after application of Baclofen (latency: 50 ± 14 sec) 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.
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