title: Inverse benzodiazepine agonist beta-CCM does not reverse learning deficit induced by sleep deprivation.
abstract: Increasing evidence indicates that sleep deprivation (SD) alters responses to pharmacological agents by affecting specific transmitter systems. The present work addressed deficits in passive avoidance (PA) performance that are seen after SD, and investigated whether treatment with the inverse benzodiazepine agonist beta-CCM could prevent such deficits. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24h (SR group). Animals were treated with saline or 0.5mg/kg beta-CCM before PA training, and were tested 30 min or 24h later. A separate set of animals was sacrificed for [(3)H]Ro 15-4513 binding analysis. beta-CCM increased PA performance in control animals in both short and long term retention tests, whereas SD and SR animals were unaffected by the drug treatment. Interestingly, [(3)H]Ro 15-4513 binding was reduced in the entorhinal cortex in both SD and SR groups. These findings suggest that the lack of promnesic effects of beta-CCM after SD and SR may be associated with benzodiazepine receptor downregulation in specific brain regions related to memory formation.
authors: Psychobiology Department, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Francisco Paulino
authors: FP
authors: Dubiela
authors: Maria Gabriela Menezes de
authors: MG
authors: Oliveira
authors: Karin Di Monteiro
authors: KM
authors: Moreira
authors: José N
authors: JN
authors: Nobrega
authors: Sergio
authors: S
authors: Tufik
authors: Débora Cristina
authors: DC
authors: Hipólide
mesh_terms: D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning / Q000187:drug effects*; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D002243:Carbolines / Q000494:pharmacology*; D054314:Drug Inverse Agonism; D058787:GABA-A Receptor Antagonists; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D012892:Sleep Deprivation
chemical_list: D001386:Azides; D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D001569:Benzodiazepines; C042957:Ro 15-4513; C036150:beta-carboline-3-carboxylic acid methyl ester