title: Infusion of adenylyl cyclase inhibitor SQ22,536 into the medial pontine reticular formation of rats enhances rapid eye movement sleep.
abstract: Microinjection of cholinergic and adenosinergic agonists into the medial pontine reticular formation of rats produces long lasting increases in the time spent in rapid eye movement sleep. Several G-protein-coupled muscarinic and adenosinergic receptors share a common action of inhibition of adenylyl cyclase and inhibition of cyclic adenosine monophosphate. Inhibition of cyclic adenosine monophosphate has been implicated in the mechanism of rapid eye movement sleep induction in the cat. We sought to determine whether a direct inhibitor of adenylyl cyclase microinjected into the rat reticular formation at sites where muscarinic and adenosinergic agonists are effective in producing long lasting elevations in rapid eye movement sleep also result in similar effects on the sleep/wake cycle. The caudal, oral pontine reticular formation was unilaterally infused with 60 nl volumes of carbachol (0.1-1.1mM) and N(6)-cyclohexyladenosine (0.1mM) each within 1h of lights on. Sites effective for significantly elevating rapid eye movement sleep for the 8h following microinjection of both receptor agonists were additionally injected with the adenylyl cyclase inhibitor, SQ22,536 (0.1M). Pontine injections of SQ22,536 resulted in significant mean increases in rapid eye movement sleep time and rapid eye movement sleep period frequency at all of these sites. As with the receptor agonists, SQ22,536 did not alter latency to rapid eye movement sleep onset. Rapid eye movement sleep amounts were observed to be significantly elevated by SQ22,536 at two days, but not at four days, following a single microinjection. These data implicate inhibition of cyclic adenosine monophosphate in the pons of the rat as a mechanism involved in the long-term modulation of rapid eye movement sleep. This mechanism may underlie the homeostatic regulation exhibited by this sleep-state.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. gmarks@mednet.swmed.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Marks
authors.forename: C G
authors.initials: CG
authors.lastname: Birabil
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D011149:Pons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012154:Reticular Formation / Q000166:cytology / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D000225:Adenine