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Increase of waking and reduction of NREM and REM sleep after nitric oxide synthase inhibition: prevention with GABA(A) or adenosine A(1) receptor agonists.
Monti, J M; Jantos, H; Monti, D.
Afiliação
  • Monti JM; Department of Pharmacology and Therapeutics, Clinics Hospital, 2833/602 Zudañez Street, Montevideo 11300, Uruguay. jmonti@mednet.org.uy
Behav Brain Res ; 123(1): 23-35, 2001 Aug 27.
Article em En | MEDLINE | ID: mdl-11377727
The effect of N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of enzyme nitric oxide synthase (NOS), on spontaneous sleep during the light period, was studied in adult rats implanted for chronic sleep recordings. L-NAME was injected by subcutaneous (s.c.) route or was infused directly into the dorsal raphe nucleus (DRN). Subcutaneous (46.0--185.0 micromol/kg) administration of L-NAME increased waking (W), slow wave sleep (SWS) and rapid-eye-movement sleep (REMS) latency, whereas SWS, REMS and the number of REM periods were reduced. Direct application of L-NAME into the DRN (0.37--1.1 micromol) induced an increment of W and a reduction of SWS and REMS. Values corresponding to SWS and REMS latency, and the number of REM periods remained within control levels. Subcutaneous administration of the GABA(A) receptor agonist muscimol (1.7--3.5 micromol/kg) or the adenosine A(1) receptor agonist L-PIA [L(-)N(6)-(2-phenylisopropyl)adenosine] (0.1--0.3 micromol/kg) induced slight but inconsistent changes of W, light sleep (LS), SWS and REMS that did not attain significance. Pretreatment with muscimol (1.7--3.5 micromol/kg, s.c.) or L-PIA (0.1--0.3 micromol/kg, s.c.) antagonized the increase of W and reduction of SWS and REMS induced by s.c. (92.0 micromol/kg) or intra-DRN (0.74 micromol) administration of L-NAME. However, neither muscimol nor L-PIA prevented the increase of REMS latency induced by L-NAME 92.0 micromol/kg, s.c. Our findings tend to indicate that the change of behavioral state observed after systemic or intra-DRN administration of L-NAME is partly related to the reduction of GABA and adenosine at critical sites in the CNS.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sono / Sono REM / Vigília / Agonistas GABAérgicos / Óxido Nítrico Sintase / NG-Nitroarginina Metil Éster / Inibidores Enzimáticos / Agonistas de Receptores de GABA-A / Agonistas do Receptor Purinérgico P1 Limite: Animals Idioma: En Revista: Behav Brain Res Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Holanda
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sono / Sono REM / Vigília / Agonistas GABAérgicos / Óxido Nítrico Sintase / NG-Nitroarginina Metil Éster / Inibidores Enzimáticos / Agonistas de Receptores de GABA-A / Agonistas do Receptor Purinérgico P1 Limite: Animals Idioma: En Revista: Behav Brain Res Ano de publicação: 2001 Tipo de documento: Article País de afiliação: Uruguai País de publicação: Holanda