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.

Postnatal exposure to fluoxetine led to cognitive‐emotional alterations and decreased parvalbumin positive neurons in the hippocampus of juvenile Wistar rats

“…Thus, we added the evaluation of behaviour in the PMDAT, which allows the concomitant evaluation of anxiety‐like behaviour and memory. Previous studies have shown that the adequate performance in this task depends on intact hippocampus (Leão, Medeiros, et al, 2016) and amygdala (Ribeiro et al, 2011), and is susceptible to variations in anxiety levels (Leão, Cabral, et al, 2016; Silva & Frussa‐Filho, 2000).…”

“…On the other hand, the performance in the PMDAT can be impaired by bidirectional alterations in the anxiety levels (Leão, Cabral, et al, 2016; Silva & Frussa‐Filho, 2000). In this respect, we observed effects of postnatal fluoxetine on anxiety‐like behaviour only in female juvenile rats.…”

Long-term Potentiation Decay and Poor Long-lasting Memory Process in the Wild Rodents Proechimys from Brazil’s Amazon Rainforest

“…In turn, memory was assessed by time spent in the aversive enclosed arm during the test sessions (Silva and Frussa-Filho, 2000 ; Rachetti et al, 2013 ; Leão et al, 2016b ). Anxiety-like behavior was given by the percent time spent in the open arms (amount of time the animal remained in the open arms/total time spent in both open and closed arms) of the device (Silva et al, 2000 ; Calzavara et al, 2004 ; Leão et al, 2016a ).…”

Memory and anxiety-like behavior of rats in the plus-maze discriminative avoidance task: Role of serotonergic transmission in the basolateral amygdala.

“…Therefore, it is possible to verify whether the effects of different manipulations or baseline conditions on emotionality would be involved with processes of aversive memory acquisition, consolidation, and/or retrieval. In parallel, motor activity of the animals can be registered independently of cognitive and anxiety-like parameters, which is relevant because motor alterations can influence the performance of animals in memory and anxiety tests (Campêlo et al, 2017; de Macêdo Medeiros et al, 2014; Kameda et al, 2007; Leão et al, 2016).…”

“…Several studies have shown the effectiveness of PMDAT to investigate bidirectional changes in aversive memory, anxiety-like and motor behaviors, as well as interactions between those phenomena (Campêlo et al, 2017; de Macêdo Medeiros et al, 2014; Leão et al, 2016; Ribeiro et al, 2011; Silva et al, 1997; Silva & Frussa-Filho, 2000). Specifically, previous studies have shown that the BLA, via GABAergic (Ribeiro et al, 2011) and cannabinoid (Munguba et al, 2011) systems, modulates aversive memory formation in the PMDAT.…”