Comparison of the elevated plus and elevated zero mazes in treated and untreated male Sprague–Dawley rats: Effects of anxiolytic and anxiogenic agents (original) (raw)
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Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat
Journal of Neuroscience Methods, 1985
A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated 4--maze consisting of two open arms and two enclosed arms. The use of this test for detecting such drug effects was validated behaviourally, physiologically, and pharmacologically. Rats made significantly fewer entries into the open arms than into the closed arms, and spent significantly less time in open arms. Confinement to the open arms was associated with the observation of significantly more anxiety-related behaviours, and of significantly greater plasma corticosterone concentrations, than confinement to the closed arms. Neither novelty nor illumination was a significant contributor to the behaviour of the rats on the +-maze. A significant increase in the percentage of time spent on the open arms and the number of entries into the open arms was observed only within clinically effective anxiolytics (chlordiazepoxide, diazepam and, less effectively, phenobarbitone). Compounds that cause anxiety in man significantly reduced the percentage of entries into, and time spent on, the open arms (yohimbine, pentylenetetrazole, caffeine, amphetamine). Neither antidepressants nor major tranquilisers had a specific effect. Exposure to a holeboard immediately before placement on the +-maze showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
Pharmacology Biochemistry and Behavior, 1986
PELLOW, S AND S E FILE Anxtolytw and anxtogemc drug effects on exploratory acttvtty tn an elevated plus-maze A no~el te~t oJ anrwty tn the rat PHARMACOL BIOCHEM BEHAV 24(3) 525-529, 1986--The current studtes further investigated the effects, mammal models of anxiety, of novel putatwe anx,olyt,c and anx~ogemc compounds beheved to reduce their effects by actions at the GABA-benzodmzepme receptor complex It was expected that the results would also provide further vahdatlon for a novel test of anx,ety based on the raUo of open to closed arm entries in an elevated plus maze m the rat The novel putative anxlolytlcs CL 218,872 (10-20 mg/kg ) and tracazolate (5 mg/kg) slgmficantly elevated the percentage of t~me spent on the open arms of an elevated plus-maze, consistent with thetr anx~olytlc act~wty in several other animal tests Also consistent w~th results from other ammal tests, no anxlolyt,c act,wty was observed for the phenylqumohne PK 8165 (10-25 mg/kg), the 3,4-benzodmzepme tofisopam (25-50 mg/kg), or busplrone (0 5-20 mg/kg) The benzodmzepme receptor reverse agonlsts FG 7142 (1-5 mg/kg) and CGS 8216 (3-10 mg/kg) had anx,ogemc actwlty in thts test, as did the atyp,cal benzodtazepme Ro 5-4864 (1-5 mg/kg) Interestingly, however, the benzodmzepme receptor antagomsts Ro 15-1788 (10-20 mg/kg) and ZK 93426 (5-10 mg/kg) had no anxlogenlc activity m thts test
The use of the elevated plus maze as an assay of anxiety-related behavior in rodents
Nature protocols, 2007
The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretched-attend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent.
Progress in neuro-psychopharmacology & biological psychiatry, 1998
1. A test battery consisting of a standard open field, an enriched open field and an elevated plus maze was used to study behavior in rats. 2. Male rats of the strains PVG/OlaHsd (PVG) and Sprague-Dawley-Hsd (SPRD) (150-200 g body wt) were used to assess interstrain differences as well as handling effects. In a subsequent experiment an other set of male PVG rats (150-200 g body wt) treated either with diazepam or zolpidem was used to evaluate the test battery for pharmacological purposes. 3. SPRD rats displayed higher motor activity levels and also higher levels of exploratory behavior than the PVG rats. In contrast plus-maze activity indicated more anxiety of SPRD than PVG rats. One week pre-test handling increased the activity of both strains but it increased explorative behavior in the enriched open field only in SPRD rats. Diazepam had a substantial anxiolytic effect. Zolpidem enhanced the explorative activity in a differently to diazepam and exerted only minor anxiolytic proper...
Ethopharmacological analysis of rat behavior on the elevated plus-maze
Pharmacology Biochemistry and Behavior, 1994
Behavioral categories were measured in rats left on an elevated plus-maze for 5 min, in addition to the traditional measures. Four independent factors emerged from a factor analysis. The variables that loaded highly and positively on Factor 1, seemingly related with anxiety, were: number of entries onto open arms, time spent on open arms, percentage of open/total arm entries, percentage of time on open arms, scanning over the edge of an open arm, and open arm end-exploring. The time spent on enclosed arms loaded highly, but negatively on the same factor. Risk-assessment from an enclosed arm also loaded negatively on Factor 1. Number of enclosed arm entries, total number of arm entries and rearing loaded highly on Factor 2, probably related to motor activity. However, the total number of entries also loaded on Factor 1, being thus a mixed index. Similarly, the number of open arm entries loaded on both Factors 1 and 2. As expected, the variables having high loads on Factor 1 were changed to one direction by administration of two anxiolytics (nitrazepam and midazolam) and to the opposite direction by two anxiogenic drugs (pentylenetetrazol and FG 7142). Such pattern of drug effects was not observed with the remaining variables. Elevated plus-maze Rats Factor analysis Anxiolytics Anxiogenic drugs
European Journal of Pharmacology, 1993
In rats naive to handling, but not in handling-habituated animals, baclofen (1 mg/kg) and (R,S) zacopride (1 ~g/kg) had significant anxiolytic effects, shown by an increased percentage of time spent on the open arms of the elevated plus-maze. The effects of buspirone were also modified by the animals' handling history and 200 p.g/kg was significantly anxiogenic only in handling-habituated animals. The pattern of results is discussed in relation to biochemical differences already reported between handling-naive and handling-habituated animals, with particular respect to changes in the 5-HT system.
Elevated mazes as animal models of anxiety: effects of serotonergic agents
Anais da Academia Brasileira de Ciências, 2007
This article reviews reported results about the effects of drugs that act upon the serotonergic neurotransmission measured in three elevated mazes that are animal models of anxiety. A bibliographic search has been performed in MED-LINE using different combinations of the key words X-maze, plus-maze, T-maze, serotonin and 5-HT, present in the title and/or the abstract, with no time limit. From the obtained abstracts, several publications were excluded on the basis of the following criteria: review articles that did not report original results, species other than the rat, intracerebral drug administration alone, genetically manipulated rats, and animals having any kind of experimental pathology. The reported results indicate that the effect of drugs on the inhibitory avoidance task performed in the elevated T-maze and on the spatio temporal indexes of anxiety measured in the X and plus mazes correlate with their effect in patients diagnosed with generalized anxiety disorder. In contrast, the drug effects on the one-way escape task in the elevated T-maze predict the drug response of panic disorder patients. Overall, the drug effects assessed with the avoidance task in the T-maze are more consistent than those measured through the anxiety indexes of the X and plus mazes. Therefore, the elevated T-maze is a promising animal model of generalized anxiety and panic disorder.
1996
Male Wistar rats were submitted to a 24-h period of social isolation combined with a 24-h period of exposure to a different vivarium, of transportation to the test room either by cart or gently carried by hand, and immediate testing in an arena and in the elevated plus-maze. Results showed that transportation by cart was aversive inasmuch as it decreased exploratory behavior in the maze. They also suggested that exploratory behavior in the closed arms of the plus-maze was also modified by aversion. This trend was reversed when the rats were also socially isolated before testing. The data suggest that less intense anxiety, as caused by social isolation or cart transportation alone, trigger mechanisms that mediate less energetic behavior, while higher levels of anxiety (as produced by the two combined) trigger mechanisms that mediate more vigorous activity. These results are comparable to others from studies showing that rats switch from active to static to explosive behaviors with increasing intensities of aversion. The elevated plus-maze test (Handley & Mithani, 1984), a modified procedure originated by Montgomery (1955), has become a known model test of animal anxiety. It was reported by Pellow and coworkers (Pellow, Chopin, File, & Briley, 1985) as a valid and reliable tool for measuring anxiety on the basis of extensive investigation analyzing several of its behavioral, physiological, and pharmacological aspects. It consists of exposing animals to a plus-shaped maze elevated above the floor, with two facing closed arms (i.e., walled and closed at the ends) and two facing open arms (i.e., not walled and not closed at the ends). A rat will explore both the closed and open arms, but will typically more frequently enter and stay longer in the closed arms. The preference ratio of open-to-closed arms, both for entries and duration of stays (Handley & Mithani, 1984; Pellow et aI., 1985), is taken as an index of anxiety-the higher the ratio, the lower the anxiety level. This test has been used to investigate anxiolytic and anxiogenic compounds and to study the involvement of neurotransmitters in anxiety (e.g.
Trial 2 in the elevated plus-maze: a different form of fear?
Psychopharmacology, 1993
A factor analysis of the scores from rats given two trials in the elevated plus-maze showed that four independent factors emerged. Measures of anxiolytic activity on trial 1 (number of open arm entries and time spent on open arms) loaded on factor 1, measures of anxiolytic activity on trial 2 loaded on factor 2, the measure of general activity (number of closed arm entries) on both trials loaded on factor 3, and a measure of decision time (time spent in central square) for both trials loaded on factor 4. The independence of trials 1 and 2 anxiety measures raises the possibility that the state of anxiety/fear on the second trial in the plus-maze is qualitatively different from that on trial 1. This difference is reflected in the loss of anxiolytic action of diazepam (2 mg/kg) on trial 2. However, this occurs only when the trials are short (5 min); when they are longer (10 min) diazepam retains anxiolytic efficacy. It is concluded that during a brief (5 rain) trial in the plus-maze rats acquire a specific phobic anxiety, which is relatively resistant to benzodiazepines. With a longer exposure to the plus-maze this form of fear extinguishes.