Anxiety elevated plus-maze test

Stress results in alterations in behavior and physiology that can be either adaptive or maladaptive. Although mice deficient in the calcium-stimulated adenylyl cyclase type VIII (ACS) exhibit indices of anxiety comparable with that of wildtype mice at baseline, ACS KO mice do not show normal increases in behavioral features of anxiety when subjected to repeated stress such as repetitive or post-restraint stress testing in the elevated plus maze test (Schaefer et al. 2000). Although these findings suggest a role for ACS in the modulation of anxiety, the mechanism by which ACS deficiency results in impaired stress-... 

It is interesting to note that pharmacological blockage of NKl receptors also revealed anxiolytic effects in the plus-maze test when mice from the 129/Sv strain (Santarelh et al. 2001), but not from other strains (Rodgers et al. 2004), were used. Thus, the anxiolytic effect of NKl receptor antagonists seems to be more sensitive to effects of the genetic background as compared to benzodiazepines. It is also possible that the relative contribution of the SP-NK1 system in the modulation of anxiety is situation dependent. The basal corticosterone levels in the blood plasma of NKIR and NK1 mice do not differ in low-stress situations, but the increase after the stressful elevated plus-maze test is blunted in the knockout animals (Santarelh et al. 2001). 

FICURE 1-1. Intracerebral infusion of antisense oligonucleotides (AS-ODN) that were targeted to the cloned CRH, and CRH2 receptor mRNA prevent translation into the receptor protein. Only a knock-down of the CRH, receptor, but not of the CRH2 receptor, reduces anxiety-related behavior in rats that were exposed to the elevated plus-maze test after central corticotropin-releasing hormone (CRH) administration. P <. 05, P <. 01. 

Kulikov, A., Aguerre, S., Berton, O., Ramos, A., Mormede, P., and Chaouloff, E., Central serotonergic systems in the spontaneously hypertensive and Lewis rat strains that differ in the elevated plus-maze test of anxiety, /. Pharmacol. Exp. Then, 281, 775, 1997. 

Recently, Benwell et al. (103) reported reductions in open-arm entries in the elevated plus-maze test when rats were tested 22 h after pretreatment with ibogaine (40 mg/kg, i.p.). In mice, ibogaine (2.5 mg/kg) exhibited anxiogenic actions, whereas a dose of 1 mg/kg had anxiolytic effects (104). These are perhaps the most compelling preclinical data that ibogaine may influence anxiety levels, because anxiolytic agents (e.g., benzodiazepines) increase open-arm entries in this test. 

Fig 2. Setup of the elevated plus-maze test of anxiety. A computerized setup that automatically monitors the time spent and number of entries into the open, center, and... 

In vivo antidepressant-like activity of lO-hydroxy-2-decenoic acid (10-HDA) in stress-inducible depression-like mouse model was conducted. The animals were evaluated by the tail-suspension test, elevated plus-maze test, and open-field test at 1 day after the end of stress exposure. The results demonstrated that 10-HDA and RJ were effective in ameliorating the stress-inducible symptoms of depression and anxiety, intraperitoneally administered, while RJ given by the oral route was less effective [80]. 

Probably the most frequently used test for unconditioned anxiety is the elevated plus maze (EPM), which was first introduced by File and coworkers (Pellow et al. 1985). The test consists of an elevated, plus-sign-shaped runway with two opposing arms being closed by walls and the other two arms being open, i.e., unprotected (Fig. 5). The animal usually is placed in the center of the EPM,... 

The elevated plus maze measures how rats and mice react in an apparatus that has two distinct environments, one a brightly lit and exposed runway and the other a dark and walled runway. The two runways intersect in the center (giving the maze the appearance of a plus sign) and are about 30 inches (76 cm) off the ground. Because rodents are nocturnal (active at night) animals and dislike open and well-lit places, the elevated plus maze is said to be a natural, or ethologically-based, test of anxiety. When a rat or mouse is placed in the elevated plus maze, it is free to go wherever it likes. This kind of approach/avoidance ... 

Figure 3.1 The elevated plus maze is a test to monitor stress, anxiety, and fear in rats and mice by measuring how they react when placed in an apparatus that has two distinct environments. The animal can choose to enter an unfamiliar area that is either brightly lit or dark. The approach/avoidance behavior displayed indicates whether the animal is under stress.

In accordance with the observation reported from pharmacological studies, FAAH / mice exhibit reduced anxiety-like behavior in two experimental models, the elevated plus maze and the light-dark test (Moreira et al., 2008). Their behavioral profile in both tests is reversed by systemic administration of rimona-bant, thus suggesting that an enhancement of CBj-receptor-mediated signaling, likely due to increased AEA tone, might be responsible for the decreased anxiety in these animals. 

Specifically, these studies found that 5-HT1A-R null animals showed increased anxiety-like behavior in the open field, elevated plus maze, elevated zero maze, and novel object tests. 5-HT1A-R KOs were also less immobile in the forced swim and tail suspension tests, the same response induced in these tests by antidepressant drugs. However, it is unclear whether this decreased immobility truly reflects an antidepressant-like coping reaction mediated by increased 5-HT transmission or whether it simply reflects an increased stress response in these anxiety-prone mutant mice (12). 

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