The elevated T-maze task as an animal model to simultaneously investigate the effects of drugs on long-term memory and anxiety in mice

Abstract

The elevated T-maze (ETM) is an apparatus derived from the elevated plus-maze test, which is used to evaluate anxiety. Because anxiety is a biasing factor in models of memory, this study proposed the ETM as a task for the simultaneous assessment of memory and anxiety in mice. The ETM consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. The anxiolytic diazepam (DZP; 1 or 2mg/kg) and the amnestic biperiden (BPR; 0.5, 1 or 3mg/kg) were injected at three distinct times: pre-training, post-training, and pre-test. Pre-training administration of BPR 1 and DZP 2 increased the number of trials needed to reach the avoidance criterion, suggesting a passive avoidance learning impairment. However, BPR induced hyperlocomotion, which could bias the interpretation of any BPR-induced effects during the training session. Pre-training injection of BPR did not affect the spontaneous increase in the latency to enter an open arm between trials, while DZP reduced latencies in the first three trials suggesting anxiolysis. In the test session, pre-training injection of BPR 1 and DZP 2 reduced latencies to enter an open arm, indicating memory impairment. Post-training and pre-test injection of DZP or BPR did not affect memory. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs.

Original article Involvement of D 2 /D 2 dopamine antagonists upon open-arms exploratory behaviours induced by intra-nucleus accumbens shell administration of N-methyl-D-aspartate

“…Due to possible misinterpretations, the available animal models for learning and memory seem to have a limited ability to detect the effect of drugs on fear and anxiety. Therefore, the proposed test-retest paradigm in the elevated plus-maze (EPM) task is an attempt to concomitantly assess the effects of drugs on anxiety, learning and memory in rodents [6]. The use of EPM in testing anxiety is based on the natural tendency of animals to avoid dangerous situations when they face height and open spaces [91].…”

Nociceptin/orphanin FQ induces simultaneously anxiolytic and amnesic effects in the mouse elevated T-maze task

“…The experimental protocol was based on the reports of Asth et al (2012). The ETM was made of wood and had three arms of equal dimensions (30×6 cm).…”

“…Aside from the limited number of studies, some reports employed the ETM task as an animal model of memory in rats (Santos et al 2006;Cruz-Morales et al 2008;do Maia et al 2010) and mice (Takahashi et al 2005;Asth et al 2012). Despite differences in protocols used, it has been observed that exposure to stress, striatal serotonin modulation (CruzMorales et al 2008), exposure to ethanol and methylmercury in rats during central nervous system development (do Maia et al 2010), and microinjections of antagonist 7-chlorokynurenic acid (Santos et al 2006) impair aversive memory in the rat ETM.…”

“…More recently, our research group has shown that a modified version of the mouse ETM task was sensitive to both anxiety-and memory-modulating drugs. The muscarinic M1 receptor antagonist biperiden impaired memory process, while leaving anxiety-like behaviors unchanged (Asth et al 2012). However, the administration of diazepam, a standard anxiolytic drug, reduced anxiety and at higher doses impaired memory process in the ETM task (Asth et al 2012).…”

“…The elevated T-maze (ETM), a derivation of the elevated plus maze (Pellow et al 1985), is a useful animal model for testing anxiety and memory simultaneously (Graeff et al 1993;Asth et al 2012), and it has been demonstrated that the critical motivational factor in this ethologically based model is the aversive nature of the open arms (Zangrossi and Graeff 1997). It should be mentioned that the ETM test was previously validated for assessing the effects of anxiolytic drugs, such as acute administration of benzodiazepines, buspirone, and ritanserin, besides the chronic administration of antidepressants (Graeff et al 1998;Teixeira et al 2000;Ruzza et al 2012).…”