Inverse benzodiazepine agonist beta-CCM does not reverse learning deficit induced by sleep deprivation

Increasing evidence indicates that sleep deprivation (0) 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 24 h (SR group). Animals were treated with saline or 0.5 mg/kg beta-CCM before PA training, and were tested 30 min or 24 h 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, [3H]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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.AFIPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FADAFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilCtr Addict & Mental Hlth, Neuroimaging Res Sect, Toronto, ON, CanadaUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilUniversidade Federal de São Paulo, Dept Psychobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, BrazilFAPESP: 98/1403-3FAPESP: 02/12453-5Web of Scienc