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

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, 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 similar to 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.