title: Diazepam effects on aversive memory retrieval and extinction: Role of anxiety levels.
abstract: Benzodiazepines (BDZs) are anxiolytic drugs that impair memory acquisition. Previous studies using the plus-maze discriminative avoidance task (PMDAT, which assesses memory and anxiety concomitantly) indicated that the effects of BDZs on anxiety and acquisition are related to each other. The possible influence of the anxiolytic action of BDZs on their effects on memory retrieval and extinction are poorly understood. This is relevant considering the relationship between aversive memories and anxiety disorders. We designed a modified protocol of PMDAT that evaluates anxiety during retrieval and extinction of the task. Male Wistar rats were trained in the PMDAT (plus-maze with two open and two enclosed arms) using a standard or a modified protocol. In the standard protocol, the aversive stimuli were presented in one of the enclosed arms during training, and the animal had free access to the whole apparatus. In the modified protocol, the open arms were blocked with glass walls. Twenty-four hours after training, the animals subjected to each of the protocols were treated with saline or 2.0mg/kg of diazepam (DZP) 30min before the test. There was a third session in the maze (retest) 24h after the test. During the test, DZP impaired and improved retrieval in rats that had been trained in the standard and the modified protocol when compared to the respective saline-treated groups. In addition, treatment with DZP prior to the test induced anxiolysis, but only in the animals that were not pre-exposed to the open arms of the apparatus (modified protocol). In these animals, DZP impaired extinction, which was evaluated during retest session. The impairing effect of DZP on extinction seems to be related to its anxiolytic action during the test (extinction learning). Further, we suggest that aversive memory retrieval depends on both the treatment and the arousal elicited by exposure to the apparatus.
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Anderson H F F
authors.initials: AH
authors.lastname: Leão
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Alícia
authors.initials: A
authors.lastname: Cabral
authors.affiliation: Department of Cellular Biology, Embryology and Genetics, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Geison S
authors.initials: GS
authors.lastname: Izídio
authors.affiliation: Department of Biosciences, Universidade Federal de São Paulo, Santos, São Paulo, Brazil.
authors.forename: Alessandra M
authors.initials: AM
authors.lastname: Ribeiro
authors.affiliation: Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil; Laboratory of Behavioral Neuroscience, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil. Electronic address: reginahsilva@gmail.com.
authors.forename: Regina H
authors.initials: RH
authors.lastname: Silva
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D003975:Diazepam / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003975:Diazepam
keywords: Anxiety; Benzodiazepine; Extinction; Memory; One-trial tolerance; Retrieval