Influence of bupropion and calcium channel antagonists on the nicotine-induced memory-related response of mice in the elevated plus maze in mice

In this study, we investigated the effects of acute administration of nicotine on memory-related behavior in mice using the elevated plus maze test. In this test, the time necessary for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. Our results revealed that nicotine (0.035 and 0.175 mg/kg, base, sc) shortened the transfer latency relative to the saline-treated group. Moreover, we investigated the effects of bupropion (10, 20 and 40 mg/kg, ip) and L-type voltage-dependent calcium channel antagonists (nimodipine, flunarizine, verapamil, diltiazem – 5, 10 and 20 mg/kg, ip) on memory-related behavior. At all tested doses, bupropion, did not significantly affect transfer latency. However, flunarizine and verapamil (both at 10 mg/kg) resulted in a slight decrease in transfer latency, whereas nimodipine (10 mg/kg) increased transfer latency. Interestingly, both bupropion (20 mg/kg) and calcium channel blockers (5 mg/kg) attenuated the improvement of memory induced by nicotine.Our findings indicate that the cholinergic nicotinic system may play an important role in memory consolidation, and that neural calcium-dependent mechanisms can be involved in the modulation of memory-related responses induced by nicotine. The results of these studies have revealed neuronal mechanisms that are important for nicotinic modulation of cognition and will be useful for the treatments of human disorders in which cholinergic pathways have been implicated, such as psychiatric disorders and addiction.     

Memory-related effects of cholinergic receptor ligands in mice as measured by the elevated plus maze test

The purpose of our experiments was to examine the influence of cholinergic receptor ligands on memory-related behavior in mice using the elevated plus maze (EPM) test. The EPM test allows the exploration of different memory processes (acquisition and consolidation), depending on the time of drug treatment. The time necessary for mice to move from the opened arm to the enclosed arm (i.e., transfer latency, TL) was used as an index of memory. Our findings reveal that for both the processes of acquisition and consolidation, treatment with nicotine (0.035 or 0.175 mg/kg, free base, sc) shortened TL on the second day of the experiments (TL2), thus improving memory processes. Treatment with scopolamine (0.3 or 1.0 mg/kg, ip) significantly increased TL2 values, thus impairing cognitive processes. Moreover, we found that treatment with nicotine, at the non-effective doses used during testing, prevented scopolamine-induced memory impairment by inducing a decrease in TL2 values. Next, we evaluated the influence of bupropion (10 or 20 mg/kg, ip), a drug currently used for smoking cessation in humans, on memory-related behavior induced by treatment with nicotine and scopolamine. An acute injection of bupropion (10 or 20 mg/kg) prior to injection with either nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg) significantly prevented nicotine-induced memory improvement or scopolamine-induced memory impairment. Bupropion treatment can diminish the rewarding (dependence-producing) effects of nicotine and also the cognitive effects that are related to addiction. Our studies further indicate the great involvement of the cholinergic system in memory processes and the potential for the development of more effective pharmacotherapies for memory impairment-like human disorders in which the cholinergic pathways have been implicated.     

钩吻素子对大鼠焦虑行为的影响

目的进一步明确钩吻素子是否具有抗焦虑作用。方法以大鼠高架十字迷宫实验为动物模型,评价钩吻素子单次皮下注射给药和连续皮下注射给药的抗焦虑活性及特点。结果钩吻素子能显著增加大鼠进入高架十字迷宫开臂次数和在开臂的停留时间百分率(P<0.05,P<0.01);钩吻素子在实验剂量下对大鼠自主运动活性无影响(P>0.05)。结论钩吻素子可能具有抗焦虑作用。     

Involvement of cholinergic receptors in the different stages of memory measured in the modified elevated plus maze test in mice

Background and MethodsSeveral lines of evidence support a strong relationship between cholinergic pathways and memory. The aim of our experiments was to examine the mechanisms involved in the formation of different memory stages, to evaluate the impact of substances, which affect the cholinergic system in mice, with an employment of the modified elevated plus maze (mEPM) test. This test allows examining different processes of memory (acquisition, consolidation and retrieval), depending on the time of drug treatment. The time period, necessary for mice to move from the opened arm to the enclosed arm (i.e., transfer latency, TL) was used as an index of memory.ResultsOur findings revealed that in both memory acquisition and consolidation, nicotine, an agonist of cholinergic receptors (0.035 and 0.175 mg/kg, free base, sc), reduced TL on the second day of the experiment (TL2), thus improving memory. In turn, scopolamine, an antagonist of cholinergic receptors (0.3 and 1.0 mg/kg, ip), significantly increased TL2 values, impairing cognition. Subsequently, we evaluated the influence of mecamylamine, a non-selective antagonist of nicotinic cholinergic receptors (nAChRs) and of varenicline, an α4β2 partial nAChRs agonist, on memory-related behaviors induced by nicotine and scopolamine. Acute injections of mecamylamine (0.5 and 1.0 mg/kg, ip) and varenicline (0.5 and 1.0 mg/kg, ip), prior to the injections of nicotine (0.035 mg/kg) or scopolamine (1.0 mg/kg), significantly suppressed nicotine-induced memory improvement or scopolamineinduced memory impairment.ConclusionOur studies indicate that the cholinergic system plays a crucial role in memory processes. Pharmacological manipulation of cholinergic transmission can be the base to develop more effective pharmacotherapies for these memory disturbances in which cholinergic receptors are involved.     

高架﹢/〇迷宫实验:经典状态焦虑动物模型相关性研究

目的探讨高架﹢迷宫实验(elevated plus maze,EPM)与高架〇迷宫实验(elevated zero maze,EZM)作为经典状态焦虑动物模型的相关性。方法昆明小鼠(4周龄,♂/♀)依次进行EPM、EZM,实验间隔1周,采用摄像系统记录5min行为变化,包括进入时间及进入次数;最终纳入实验参数有:开臂区进入时间百分率(Otime%)和两臂区进入总次数(Entries);采用描述性分析、聚类分析、因子分析、相关分析及一致性检验进行EPM与EZM行为模式、结构维度及相关性研究。结果t检验结果显示,与EPM相比,EZM Otime%(♂/♀/♂+♀)均降低,而Entries(♂/♂+♀)均升高,且差异有统计学意义;Fiedman检验结果显示,EPM/EZM实验参数Otime%(♂/♀/♂+♀)、Entries(♂/♀/♂+♀)重复测量片段间差异均有统计学意义;Wilcoxon检验结果显示,与EPM相比,EZM Otime%在1st min(♂/♀/♂+♀)、2nd min(♂/♀/♂+♀)、3rd min(♀/♂+♀)均降低,而Entries在1st min(♂/♂+♀)、4th min(♂/♀/♂+♀)、5th min(♂+♀)均升高,且差异有统计学意义。聚类分析结果显示,EPM/EZM实验参数可分组为EPM类和EZM类(♂/♀/♂+♀)。因子分析结果显示,EPM/EZM实验参数可提取为EPM因子和EZM因子(♂/♀/♂+♀)。相关分析结果显示,EPM和EZM实验参数Otime、Entries均具有一般或者较差相关性(♂/♀/♂+♀)。一致性检验结果显示,EPM和EZM实验参数Otime%(♂/♀/♂+♀)具有一般一致性。结论尽管EPM/EZM作为状态焦虑动物模型具有相类似内在原理,但是因为其外在环境(结构)差异性,导致EPM/EZM具有不同行为模式,分属不同结构维度,且仅具有一般相关性和一致性,而稳定性实验参数则首选Otime%。     

Acute effect of Copaifera reticulata Ducke copaiba oil in rats tested in the elevated plus‐maze: an ethological analysis

Objectives Copaiba oil oleoresin exuded from Copaifera reticulata Ducke (CRD) is commonly used in anti‐inflammatory, healing and anti‐tumoral folk medicines. The purpose of this study was to investigate the putative anxiolytic effect of acute administration of CRD. Methods CRD was administered (100, 400 and 800 mg/kg, p.o.) to male Wistar rats submitted to the elevated plus‐maze model of anxiety using an ethopharmacological analysis. Key findings In comparison with control rats, CRD increased the percentage of entries in the open arms over the entire dose range tested (vehicle, 33.6 ± 4.5; CRD 100 mg/kg, 44.67 ± 3.68; CRD 400 mg/kg, 47.2 ± 2.3; CRD 800 mg/kg, 50.7 ± 2.2) and the percentage of time spent in the open arms of the elevated plus‐maze at the highest dose (800 mg/kg) (vehicle, 26.4 ± 5.7; CRD 800 mg/kg, 52.0 ± 2.7). A standard anxiolytic, diazepam (3 mg/kg, p.o.), was used as a positive control. In a similar way, diazepam increased the percentage of entries and time spent in the open arms when compared with vehicle (% open entries: vehicle, 45.4 ± 1.3; diazepam, 50.7 ± 1.9; % time spent in open arms: vehicle, 28.2 ± 0.9; diazepam, 38.9 ± 1.2). Regarding ethological measures, CRD at the highest dose (800 mg/kg) reduced peeping out (anxiety‐related behaviour) (vehicle, 3.1 ± 0.6; CRD, 0.9 ± 0.2) and increased end‐arm activity (vehicle, 0.2 ± 0.2; CRD, 2.0 ± 0.4), indicating an enhanced tendency of the rats to explore actively the potentially dangerous areas of the maze. Diazepam decreased peeping out (vehicle, 3.3 ± 0.3; diazepam, 1.0 ± 0.2) and flat‐back approach (vehicle, 0.8 ± 0.2; diazepam, 0.2 ± 0.1) and increased end‐arm activity (vehicle, 0.3 ± 0.1; diazepam, 2.5 ± 0.3) and head‐dipping (vehicle, 8.2 ± 0.4; diazepam, 12.0 ± 0.5). Conclusions These data showed, for the first time, that acute treatment with CRD copaiba oil produced a dose‐dependent anxiolytic‐like effect over the dose range tested, on conventional and ethological parameters, without adversely affecting general activity levels.     

Effects of central noradrenaline depletion by the selective neurotoxin DSP-4 on the behaviour of the isolated rat in the elevated plus maze and water maze

RATIONALE: Social isolation of the rat from weaning influences behaviour following central noradrenaline (NA) depletion by the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4). OBJECTIVES: The study characterised the effects of DSP-4 on the behaviour of isolates in the elevated plus maze and water maze. METHODS: Male Lister hooded rats were reared singly or in groups after weaning. Two weeks postweaning, the rats were injected with DSP-4 (25 mg/kg, i.p.) or saline. From week 4, rats were tested in the plus maze and in the water maze. RESULTS: DSP-4 significantly reduced cortical and hippocampal NA but had no effect on hypothalamic NA. Isolation rearing alone had no significant effects on behaviour in the elevated plus maze but enhanced retention of platform placement in the water maze as measured by increased entries to the platform annulus during the probe test. DSP-4 in group-reared rats increased activity in the open arms and increased general activity in the elevated plus maze with no effect on water maze performance. DSP-4-treated isolates spent less time in the open arms and were hypoactive in the plus maze compared to group-reared DSP-4-treated rats, and had impaired retention of spatial memory in the water maze compared to isolate controls. CONCLUSIONS: DSP-4 treatment had an 'anxiolytic' effect in group-reared rats in the elevated plus maze. In the water maze, isolation rearing enhanced retention of spatial information, an effect normalised by NA depletion. The results demonstrate the importance of noradrenergic function in the regulation of responsiveness to environmental cues.     

Nitrous oxide anxiolytic effect in mice in the elevated plus maze: Mediation by benzodiazepine receptors

In earlier research, we have hypothesized that exposure to nitrous oxide (N₂O) produces an anxiolytic effect that is mediated by benzodiazepine (BZ) receptors. The present research was conducted to characterize pharmacologically the behavioral effects of N₂O in comparison with a BZ standard, chlordiazepoxide (CP), in the mouse elevated plus maze. Exposure to increasing levels of N₂O produced a concentration-related increase in the percent of total entries into and the percent of total time spent on the open arms, a pattern of response similar to that induced by CP. These effects of N₂O and CP were both antagonized by pretreatment with the BZ receptor blocker flumazenil (FLU). In another experiment, mice made tolerant to CP also exhibited a cross-tolerance to N₂O. These results support the hypothesis that the anxiolytic effect of N₂O is mediated by BZ receptors.Portions of this paper were presented at the Third International Brain Research Organization (IBRO) World Congress of Neuroscience (Abstracts, p 211, 1991) and the 1992 Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics (ASPET) (Pharmacologist 34: 137, 1992).     

Chronic morphine and tramadol re‐exposure induced an anti‐anxiety effect in prepubertal rats exposed neonatally to the same drugs

Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety‐like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3–21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re‐exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re‐exposure to tramadol and this anxiolytic‐like behaviour was more dominant in EPM re‐exposure in rats that had received higher doses of tramadol. Re‐exposure to tramadol elicited a stronger anxiolytic‐like behaviour than re‐exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re‐exposure to these drugs at an immature stage produces considerable anxiolytic‐like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long‐term changes in the opioid response.     

Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice

Rationale (1S,2S,5R,6S)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) is a potent and selective agonist for group II metabotropic glutamate (mGlu2 and mGlu3) receptors, with anxiolytic-like activity in animal and human models, and efficacy in anxiety patients. However, the lack of mGlu2 or mGlu3 receptor specific agonists has prevented in vivo characterization of individual functions of these two receptors in mediating the anxiolytic-like effects of LY354740.Objective To utilize mGlu2 receptor and mGlu3 receptor knockout animals and the mGlu2/3 selective antagonist (2S,1S,2S)-2-(9-xanthylmethyl)-2-(2-carboxycyclopropyl)glycine (LY341495) to further investigate the roles of mGlu2 and mGlu3 receptors in mediating the anxiolytic-like actions of LY354740 in a mouse model of anxiety [elevated plus maze (EPM) test].Methods To confirm that mGlu2/3 receptors are responsible for anxiolytic-like activity in the EPM under these test conditions, mice were pretreated with LY341495 at 30 min prior to s.c. administered LY354740. Subsequently, saline vehicle or LY354740 was administered (s.c.) 30 min before the EPM testing in wild-type, mGlu2 receptor knockout, and mGlu3 receptor knockout mice.Results LY354740 reduced in a dose-dependent manner anxiety-related behavior on the EPM in wild-type mice with a maximally effective dose of 10–20 mg/kg s.c. Pretreatment with LY341495 potently prevented the anxiolytic-like effects of LY354740 (20 mg/kg, s.c.) in mice. Although the mGlu2 receptor knockout and mGlu3 receptor knockout mice were grossly normal, the anxiolytic-like activity of LY354740 (20 mg/kg, s.c.) was not evident in either mGlu2 or mGlu3 receptor knockout mice, when compared to their wild-type controls.Conclusions The activation of both mGlu2 and mGlu3 receptors by LY354740 appears to be required for anxiolytic-like activity in the EPM test in mice. These studies serve as a foundation for additional studies on underlying circuits, brain structures, and receptor subtypes involved in the anxiolytic-like actions of mGlu receptor active agents, and the design of future drugs for anxiety disorders in humans.     

GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures

Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABA_A agonists muscimol (0.5–1.0 mg/kg), THIP (2.5–10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0–20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two nonconditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100–400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states.     

NMDA receptor activation antagonizes the NMDA antagonist-induced antianxiety effect in the elevated plus-maze test in mice

BackgroundThe purpose of this study was to determine how the activation of different regulatory domains of the NMDAcomplex affects the antianxiety effect of antagonists acting at its distinct binding sites.MethodsThe anxiolytic-like activity was assessed by the elevated plus-maze test in mice.ResultsThe anxiolytic activity of CGP 37849 (a competitive NMDAreceptor antagonist) and L-701,324 (an antagonist at glycine site) was confirmed, but effects of both were significantly reduced by N-methyl-D-aspartic acid (NMDA) or by D-serine agonists at glutamate and glycine site of the NMDA receptor complex, respectively.ConclusionThe obtained data suggest that stimulation of the glutamate or glycine recognition site of the NMDAreceptor complex significantly decreases the antianxiety properties of antagonists of either site.     

脑功肽组方对高架十字迷宫大鼠海马单胺类递质及其代谢物的影响

摘 要 目的：观察脑功肽组方对高架十字迷宫大鼠海马单胺类递质及其代谢产物含量的影响,探讨脑功肽组方抗焦虑作用的机制。方法: 采用大鼠高架十字迷宫焦虑动物模型（EPM）观察脑功肽组方2个剂量组对大鼠焦虑行为学的影响;采用高效液相色谱 荧光检测（HPLC FLD）法测定大鼠海马单胺类递质及其代谢产物的含量。结果:与空白对照组相比,脑功肽组方高剂量组进入开臂次数百分比、开臂停留时间百分比均显著提高（P＜0.05）,脑功肽低剂量组大鼠进入开臂次数百分比显著提高（P＜0.05）;脑功肽高剂量组大鼠海马5 羟色胺（5 HT）的含量与空白对照组相比显著降低（P＜0.05）,高香草酸（HVA）含量显著升高（P＜0.05）。结论:在EPM实验中,脑功肽组方显示其具有一定的抗焦虑作用,大鼠海马单胺类递质含量测定显示可能与降低大鼠海马5 HT含量有关。     

One-trial tolerance to the effects of chlordiazepoxide on the elevated plus maze may be due to locomotor habituation,not repeated drug exposure

The phenomenon of one-trial tolerance to the effects of chlordiazepoxide hydrochloride (CDP) in the elevated plus maze was re-examined. Unlike previous experiments, pre-exposure to the maze resulted in habituation and a consequential reduction in time spent on the open arms. The habituation effect was measured by recording the actual distance travelled by the rats in the maze and this was found to be significantly reduced by pre-exposure. Pre-exposure to the maze in the presence of CDP resulted in a reduced response to its anxiolytic-like effects (increasing time on the open arms compared to vehicle control rats). However, although the time spent on the open arms was reduced by pre-exposure, CDP significantly increased the time spent on the open arms by rats pre-exposed under a non-drugged state. These results suggest that rats do not become tolerant to the effects of CDP, but rather the reduced response to CDP after pre-exposure is due to habituation of exploratory behaviour.     

The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus maze and the light-dark exploration test are age dependent, sexually dimorphic, and task dependent

Previous research in our laboratory revealed sexually dimorphic effects of prior exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to examine the developmental time course of this effect and determine the extent to which it generalizes to other anxiety paradigms, young adult (61-64 days old) and adult (96-107 days old) male and female rats were treated with PCP (15 mg/kg) or saline. Following a two week withdrawal period, animals were tested in either the elevated plus maze (EPM) or a light-dark exploration (LD) test. In adults, both tests revealed a sexually dimorphic effect driven by PCP-induced decreases in anxiety in females as indicated by increased time spent in the open arms of the EPM and in the lit compartment of the LD test and increased anxiety in males as indicated by decreased time spent in the lit compartment of the LD. In young animals, PCP pretreatment decreased open arm exploration in the elevated plus maze, indicating increased anxiety. However, PCP increased time spent in the light compartment in the light-dark exploration test, indicating decreased anxiety. Corticosterone levels measured 15 min after the onset of the EPM failed to reveal an association between the behavioral effects of PCP and corticosterone levels. The results in adults substantiate the previously observed sexually dimorphic effect of PCP on elevated plus maze behavior in adults and indicate that the effect generalizes to another anxiety paradigm. The results in the younger animals suggest an age dependent effect of PCP on anxiety in general and indicate that behaviors in the elevated plus maze and the light-dark exploration test reflect dissociable psychobiological states.     

Effects of the histamine H3 receptor antagonist ABT-239 on cognition and nicotine-induced memory enhancement in mice

BackgroundThe strong correlation between central histaminergic and cholinergic pathways on cognitive processes has been reported extensively. However, the role of histamine H₃ receptor mechanisms interacting with nicotinic mechanisms has not previously been extensively investigated.MethodsThe current study was conducted to determine the interactions of nicotinic and histamine H₃ receptor systems with regard to learning and memory function using a modified elevated plus-maze test in mice. In this test, the latency for mice to move from the open arm to the enclosed arm (i.e., transfer latency) was used as an index of memory. We tested whether ABT-239 (4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl), an H₃ receptor antagonist/inverse agonist, had influence on two different stages of memory, i.e., memory acquisition and consolidation (administered prior to or immediately after the first trial, respectively) and whether ABT-239 influenced nicotine-induced memory enhancement.ResultsOur results revealed that the acute administration of nicotine (0.035 and 0.175 mg/kg), but not of ABT-239 (0.1–3 mg/kg) reduced transfer latency in the acquisition and consolidation phases. In combination studies, concomitant administration of either ABT-239 (1 and 3 mg/kg) and nicotine (0.035 mg/kg), or ABT-239 (0.1 mg/kg) and nicotine (0.0175 mg/kg) further increased nicotine-induced improvement in both memory acquisition and consolidation.ConclusionThe present data confirm an important role for H₃ receptors in regulating nicotine-induced mnemonic effects since inhibition of H₃ receptors augmented nicotine-induced memory enhancement in mice.     

Effects of repeated ethanol administration in the plus maze; a simple model for conditioned abstinence behaviour

Classical conditioning is considered to be an important factor in drug dependence. Exposure to an environment in which alcohol has been repeatedly consumed may produce feelings of anxiety and dysphoria in a currently abstinent patient, and may precipitate relapse drinking. The present study modeled this process, by repeatedly exposing mice to an elevated plus maze after ethanol administration. When ethanol injections and maze exposure were repeated for 9 days, and the ethanol injections replaced by saline on the tenth day, mice consistently exhibited a characteristic behaviour pattern, with increased stretched attend postures and proportion of time spent in the central square. This behaviour was different from that previously seen during withdrawal from ethanol, and was not observed when repeated injections of ethanol were given either without, or after, maze exposure. Thus the characteristic behaviour pattern appeared to be contingent on the animals being repeatedly exposed to the maze environment while under the influence of ethanol. In particular, the reduction in stretched attend postures produced by acute ethanol, the tolerance to this behaviour seen after repeated ethanol and the increase in it after replacement of ethanol by saline, are consistent with the pattern predicted for a behavioural response to the absence of ethanol, conditioned to the environment of the maze. Received: 21 May 1998/Final version: 4 September 1998     

Comparison of the elevated plus and elevated zero mazes in treated and untreated male Sprague-Dawley rats: Effects of anxiolytic and anxiogenic agents

The elevated plus and zero mazes (Plus and Zero, respectively) are used to assess behavior related to anxiety in rodents but direct comparisons of the two tests are lacking for rats. We compared the two methods in adult male Sprague-Dawley rats. Untreated rats in the Zero spent more time in open zones and exhibited more head dips than in the Plus whereas start latency and closed area entries were lower in the Zero than in the Plus. Diazepam (1 mg/kg) exposure increased time in the open in both mazes. Restraint (60 min prior to testing), yohimbine (2.5 mg/kg), and caffeine (100 mg/kg) had the opposite effect, significantly decreasing time spent in open zones in both mazes. No sexual dimorphism in behavior was seen in either maze in untreated rats. Although more open area time was evident in untreated animals in the Zero, after drug challenge both mazes detected anxiolytic and anxiogenic effects equally. Zero maze data can be analyzed directly because no center region exists; otherwise the two methods appear comparable following challenge.