Inverse benzodiazepine agonist beta-CCM does not reverse learning deficit induced by sleep deprivation.
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.
Dubiela
Francisco Paulino
FP
Psychobiology Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Oliveira
Maria Gabriela Menezes de
MG
Moreira
Karin Di Monteiro
KM
Nobrega
José N
JN
Tufik
Sergio
S
Hipólide
Débora Cristina
DC
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
D001386:Azides; D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D001569:Benzodiazepines; C042957:Ro 15-4513; C036150:beta-carboline-3-carboxylic acid methyl ester