Microinjection of the nitric oxide synthase inhibitor L-NAME into the lateral basal forebrain alters the sleep/wake cycle of the rat.
The effects of N(G)-nitro-L-arginine methyl ester (L-NAME) (0.19-0.74 micromol), a competitive inhibitor of the enzyme nitric oxide synthase (NOS); L-arginine (48.0-191.0 nmol), a nitric oxide (NO) precursor; and molsidomine (0.06-0.24 nmol), an NO donor, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Direct bilateral application of L-NAME into the nucleus of the horizontal limb of the diagonal band of Broca (HDB) increased waking (W) and reduced slow wave sleep (SWS). On the other hand, intra-HDB injection of L-arginine or molsidomine induced slight but inconsistent changes of sleep variables that did not attain significance. Pretreatment with L-arginine (191.0 nmol) or molsidomine (0.24 nmol) prevented the increase of W and the reduction of SWS induced by L-NAME (0.37 micromol), thus indicating that a decrease in the availability of NO may be involved in the effects of L-NAME on sleep variables. An increase in the release of acetylcholine (ACh) and/or a reduction in the output of gamma-aminobutyric acid (GABA) and adenosine could tentatively explain the effects of L-NAME on SWS and W.
Monti
Jaime M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11300, Uruguay. jmonti@mednet.org.uy
Jantos
Héctor
H
D000109:Acetylcholine / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal; D020667:Diagonal Band of Broca / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D008981:Molsidomine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D016548:Prosencephalon / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C026512:arginine methyl ester; D005680:gamma-Aminobutyric Acid; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000241:Adenosine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester