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This Article Full Text Full Text (PDF) All Versions of this Article: 97/6/3841    most recent 00263.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Datta, S. Search for Related Content PubMed PubMed Citation Articles by Datta, S.

Activation of Pedunculopontine Tegmental PKA Prevents GABA_B Receptor Activation–Mediated Rapid Eye Movement Sleep Suppression in the Freely Moving Rat

Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts

Submitted 8 March 2007; accepted in final form 3 April 2007

The pedunculopontine tegmental (PPT) GABAergic system plays a crucial role in the regulation of rapid eye movement (REM) sleep. I recently reported that the activation of PPT GABA_B receptors suppressed REM sleep by inhibiting REM-ON cells. One of the important mechanisms for GABA_B receptor activation–mediated physiological action is the inhibition of the intracellular cAMP-dependent protein kinase A (cAMP-PKA) signaling pathway. Accordingly, I hypothesized that the PPT GABA_B receptor activation–mediated REM sleep suppression effect could be mediated through inhibition of cAMP-PKA activation. To test this hypothesis, a GABA_B receptor selective agonist, baclofen hydrochloride (baclofen), cAMP-PKA activator, Sp-adenosine 3',5'-cyclic monophosphothioate triethylamine (SpCAMPS), and vehicle control were microinjected into the PPT in selected combinations to determine effects on sleep-waking states of chronically instrumented, freely moving rats. Microinjection of SpCAMPS (1.5 nmol) induced REM sleep within a short latency (12.1 ± 3.6 min) compared with vehicle control microinjection (60.0 ± 6.5 min). On the contrary, microinjection of baclofen (1.5 nmol) suppressed REM sleep by delaying its appearance for 183 min; however, the suppression of REM sleep by baclofen was prevented by a subsequent microinjection of SpCAMPS. These results provide evidence that the activation of cAMP-PKA within the PPT can successfully block the GABA_B receptor activation–mediated REM sleep suppression effect. These findings suggest that the PPT GABA_B receptor activation–mediated REM sleep regulating mechanism involves inactivation of cAMP-PKA signaling in the freely moving rat.