Activation of pedunculopontine tegmental PKA prevents GABAB receptor activation-mediated rapid eye movement sleep suppression in the freely moving rat

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Abstract

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 GABAB receptors suppressed REM sleep by inhibiting REM-ON cells. One of the important mechanisms for GABAB 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 GABAB receptor activation-mediated REM sleep suppression effect could be mediated through inhibition of cAMP-PKA activation. To test this hypothesis, a GABAB receptor selective agonist, baclofen hydrochloride (baclofen), cAMP-PKA activator, Spadenosine 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 GABAB receptor activation-mediated REM sleep regulating mechanism involves inactivation of cAMP-PKA signaling in the freely moving rat.

Original languageEnglish (US)
Pages (from-to)3841-3850
Number of pages10
JournalJournal of neurophysiology
Volume97
Issue number6
DOIs
StatePublished - Jun 1 2007

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REM Sleep
Cyclic AMP-Dependent Protein Kinases
Sleep
Baclofen
Microinjections
GABA-B Receptors

All Science Journal Classification (ASJC) codes

  • Physiology
  • Neuroscience(all)

Cite this

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title = "Activation of pedunculopontine tegmental PKA prevents GABAB receptor activation-mediated rapid eye movement sleep suppression in the freely moving rat",
abstract = "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 GABAB receptors suppressed REM sleep by inhibiting REM-ON cells. One of the important mechanisms for GABAB 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 GABAB receptor activation-mediated REM sleep suppression effect could be mediated through inhibition of cAMP-PKA activation. To test this hypothesis, a GABAB receptor selective agonist, baclofen hydrochloride (baclofen), cAMP-PKA activator, Spadenosine 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 GABAB receptor activation-mediated REM sleep regulating mechanism involves inactivation of cAMP-PKA signaling in the freely moving rat.",
author = "Subimal Datta",
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T1 - Activation of pedunculopontine tegmental PKA prevents GABAB receptor activation-mediated rapid eye movement sleep suppression in the freely moving rat

AU - Datta, Subimal

PY - 2007/6/1

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N2 - 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 GABAB receptors suppressed REM sleep by inhibiting REM-ON cells. One of the important mechanisms for GABAB 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 GABAB receptor activation-mediated REM sleep suppression effect could be mediated through inhibition of cAMP-PKA activation. To test this hypothesis, a GABAB receptor selective agonist, baclofen hydrochloride (baclofen), cAMP-PKA activator, Spadenosine 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 GABAB receptor activation-mediated REM sleep regulating mechanism involves inactivation of cAMP-PKA signaling in the freely moving rat.

AB - 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 GABAB receptors suppressed REM sleep by inhibiting REM-ON cells. One of the important mechanisms for GABAB 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 GABAB receptor activation-mediated REM sleep suppression effect could be mediated through inhibition of cAMP-PKA activation. To test this hypothesis, a GABAB receptor selective agonist, baclofen hydrochloride (baclofen), cAMP-PKA activator, Spadenosine 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 GABAB receptor activation-mediated REM sleep regulating mechanism involves inactivation of cAMP-PKA signaling in the freely moving rat.

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