title: Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep-like depression of hypoglossal motoneuronal activity.
abstract: Recently, we reported that the suppression of hypoglossal (XII) motoneuronal activity that occurs during the carbachol-induced, rapid eye movement (REM) sleep-like state is abolished by the microinjection into the XII nucleus of a drug mix that antagonizes aminergic excitation and amino acid-mediated inhibition (prazosin, methysergide, bicuculline and strychnine). We now assess the role of glycinergic inhibition in the depression of XII motoneuronal activity and estimate the distribution of the antagonists around the XII nucleus at the time when they are effective. Towards the first goal, REM sleep-like episodes were elicited in urethane-anesthetized rats by 10 nl carbachol microinjections into the dorsomedial pons prior to, and at different times after, combined microinjections into the XII nucleus of only three antagonists (strychnine omitted). As in our previous study, the carbachol-induced depression of XII activity was abolished during tests performed 42-88 min after the antagonists, whereas other characteristic effects of carbachol (appearance of hippocampal theta, cortical activation, decreased respiratory rate) remained intact. The depressant effect of carbachol on XII motoneurons partially recovered after 2.5 h. Towards the second goal, using a drug diffusion model, we determined that the tissue concentrations of the antagonists at the time when they were effective were within the range of their selective actions, and the drugs acted within 0.9-1.4 mm from the injection sites, thus within a space containing XII motoneurons and their dendrites. We conclude that antagonism of alpha-adrenergic, serotonergic, and GABA(A) receptors are sufficient to abolish the REM sleep-like atonia of XII motoneurons.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104-6046, USA. vfenik@vet.upenn.edu
authors.forename: Victor B
authors.initials: VB
authors.lastname: Fenik
authors.forename: Richard O
authors.initials: RO
authors.lastname: Davies
authors.forename: Leszek
authors.initials: L
authors.lastname: Kubin
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018684:Glycine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007002:Hypoglossal Nerve / Q000187:drug effects* / Q000503:physiopathology*; D007267:Injections; D008297:Male; D008845:Microinjections; D009046:Motor Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011149:Pons / Q000187:drug effects; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects; D013331:Strychnine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000317:Adrenergic alpha-Antagonists; D018679:Cholinergic Agonists; D018756:GABA Antagonists; D018684:Glycine Agents; D012702:Serotonin Antagonists; D002217:Carbachol; D013331:Strychnine; D009638:Norepinephrine; D011224:Prazosin; D001640:Bicuculline