The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
R J Rodgers - One of the best experts on this subject based on the ideXlab platform.
-
behavioral profile of wild mice in the Elevated Plus Maze test for anxiety
Physiology & Behavior, 2000Co-Authors: A Holmes, Stefano Parmigiani, Pier Francesco Ferrari, Paola Palanza, R J RodgersAbstract:Systematic observations of the defensive behavior of wild rodents have greatly informed the experimental study of anxiety and its neural substrates in laboratory animals. However, as the former work has been almost exclusively carried out in rats, few data are available concerning the reactivity of wild mice to standardized tests of anxiety-related behavior. In the present experiments, we employed ethological measures to examine the behavioral responses of a wild-derived population of house mice (Mus musculus) in the Elevated Plus-Maze. In direct comparisons with laboratory Swiss mice, male wild mice exhibited substantially Elevated levels of exploratory activities and an overall "preference" for the open arms of the Plus-Maze. On re-exposure to the Plus-Maze, male wild mice showed further increases in open arm exploration, while Swiss mice showed a marked shift to the enclosed parts of the Plus-Maze. Tested over a single session, female wild mice also exhibited a profile of high open arm exploration, but showed levels of exploratory behaviors and locomotor activity similar to female Swiss counterparts. While exploratory patterns in wild mice show similarities to profiles seen in certain laboratory strains (e.g., BALB/c), wild mice displayed a number of additional behaviors that are unprecedented in Plus-Maze studies with laboratory mice. These included actual and attempted jumps from the Maze, spontaneous freezing, and exploration of the upper ledges of the closed arms. Thus, while in conventional terms the behavior of wild mice was consistent with one of low anxiety-like behavior, the presence of these unique elements instead indicates a profile more accurately characterized by high reactivity and escape motivation. We discuss how the use of an ethological approach to measuring Plus-Maze behavior can support accurate interpretation of other exceptional profiles in this test, such as those possibly arising from phenotyping of transgenic and gene knockout mice.
-
anxiety defence and the Elevated Plus Maze
Neuroscience & Biobehavioral Reviews, 1997Co-Authors: R J Rodgers, A DalviAbstract:The Elevated Plus-Maze test has been in use as a rodent model of anxiety for a decade, and is representative of those tests that are based upon the study of spontaneous behaviour patterns and which have high ecological validity. The origins of the test in studies of the relationship between exploration and fear are reviewed, and attention is drawn to the distinct possibility that variation in the pharmacosensitivity of the procedure may be attributable to often extreme methodological variation between laboratories. In considering further this issue, attention is also drawn to the need to collect data under constant test conditions and to provide the minimum database necessary to reach conclusions regarding the behavioural specificity of drug action. Recent research, which has extended the conventional Plus-Maze scoring technique to include specific behavioural acts and postures (in particular, those relating to defensive behaviour), is described. The value of such an ethological approach to the Plus-Maze is then exemplified with original data that demonstrate behaviourally selective, anti-anxiety effects of the GABAA receptor agonist, muscimol (0.125-1.0 mg/kg). It is concluded that, when used appropriately, the Elevated Plus-Maze test can be a very valuable tool in drug screening and in the study of the neurobiology of anxiety and defence. More attention to behaviour and somewhat less emphasis on test simplicity and convenience would seem to be warranted.
-
behavioural effects in mice of subchronic chlordiazepoxide maprotiline and fluvoxamine ii the Elevated Plus Maze
Pharmacology Biochemistry and Behavior, 1997Co-Authors: R J Rodgers, M G Cutler, J E JacksonAbstract:Abstract In view of apparent commonalities in the aetiology, symptomatology, and pharmacotherapy of anxiety and depressive disorders, the present study compares the effects of the benzodiazepine, chlordiazepoxide (1.0–8.0 mg/kg), the selective noradrenaline (NA) reuptake inhibitor, maprotiline (0.5–10.0 mg/kg), and the serotonin (5-HT)-selective reuptake inhibitor, fluvoxamine (2.0–8.0 mg/kg), on the behaviour of mice in the Elevated Plus-Maze test of anxiety. To more accurately reflect the clinical situation, subjects were treated daily for 21 days prior to testing, and comprehensive behavioural profiles were obtained through the application of an ethological scoring technique. Results show that subchronic treatment with chlordiazepoxide produced clear anxiolytic-like effects at the highest dose tested, coupled with an inhibition of risk assessment over the entire dose range. With the exception of risk assessment measures, anxiolytic-like effects were also seen with a low dose (0.5 mg/kg) of maprotiline; these effects were lost at higher doses. In contrast to these data, fluvoxamine produced minimal behavioural change under present test conditions. Findings are discussed in relation to the relative efficacy of selective monoamine reuptake inhibitors in the treatment of anxiety disorders, and the nature of anxiety evoked in mice by exposure to the Elevated Plus-Maze.
-
behavioural effects in mice of subchronic buspirone ondansetron and tianeptine ii the Elevated Plus Maze
Pharmacology Biochemistry and Behavior, 1997Co-Authors: R J Rodgers, M G Cutler, J E JacksonAbstract:In follow-up to recent work on benzodiazepines (chlordiazepoxide) and selective monoamine reuptake inhibitors (maprotiline and fluvoxamine), the present study compares the effects of the 5-HT1A receptor partial agonist, buspirone (0.75–3.0 mg/kg), the 5-HT3 receptor antagonist, ondansetron (0.1–100 μg/kg), and the novel antidepressant, tianeptine (2.5–10.0 mg/kg), on the behaviour of mice in the Elevated Plus-Maze test of anxiety. Compounds were administered daily for 21 days prior to testing, and an ethological scoring technique was used to generate comprehensive behavioural profiles. Results show that subchronic treatment with ondansetron failed to influence the behaviour of mice in the Plus-Maze, while the limited changes induced by buspirone could not be attributed to anxiety-related processes. In contrast, tianeptine produced unambiguous anxiogenic-like effects at the top dose tested (10.0 mg/kg), a profile that was not secondary to changes in general levels of locomotor activity or exploration. Data are discussed in relation to current pharmacotherapy of anxiety and depressive disorders, and the nature of anxiety induced by animal models.
-
factor analysis of spatiotemporal and ethological measures in the murine Elevated Plus Maze test of anxiety
Pharmacology Biochemistry and Behavior, 1995Co-Authors: R J Rodgers, N J T JohnsonAbstract:Recent research employing the Elevated Plus-Maze to assess anxiety in rodents has incorporated a variety of behavioral elements in addition to the standard parameters of entries onto and time spent in the aversive open arms. In the present study, we have used a large database comprising the behavioral profiles of 90 undrugged mice to examine the relationship between the standard spatiotemporal measures and a range of specific behaviors related to the defensive repertoire of the mouse. A factor analysis applied to the standard measures revealed two factors related to anxiety and locomotor activity. The simple addition of center time (an infrequently recorded measure) to the analysis yielded a third factor, most probably related to decision making. A large-scale factor analysis applied to all measures further confirmed the existence of factors related to anxiety, locomotor activity, and decision making, and revealed three further factors thought to represent risk assessment, vertical activity, and exploratory behavior. Thus, the inclusion of ethological measures not only confirmed prior knowledge based on a very limited range of measures, but also demonstrated the existence of additional behavioral dimensions. The potential applications of this knowledge are discussed.
Silvio Morato - One of the best experts on this subject based on the ideXlab platform.
-
a computational model for exploratory activity of rats with different anxiety levels in Elevated Plus Maze
Journal of Neuroscience Methods, 2014Co-Authors: Ariadne De Andrade Costa, Silvio Morato, Antonio C Roque, Renato TinosAbstract:The Elevated Plus-Maze is an apparatus widely used to study the level of anxiety in rodents. The Maze is Plus-shaped, with two enclosed arms and two open arms, and Elevated 50cm from the floor. During a test, which usually lasts for 5min, the animal is initially put at the center and is free to move and explore the entire Maze. The level of anxiety is measured by variables such as the percentage of time spent and the number of entries in the enclosed arms. High percentage of time spent at and number of entries in the enclosed arms indicate anxiety. Here we propose a computational model of rat behavior in the Elevated Plus-Maze based on an artificial neural network trained by a genetic algorithm. The fitness function of the genetic algorithm is composed of reward (positive) and punishment (negative) terms, which are incremented as the computational agent (virtual rat) moves in the Maze. The punishment term is modulated by a parameter that simulates the effects of different drugs. Unlike other computational models, the virtual rat is built independently of prior known experimental data. The exploratory behaviors generated by the model for different simulated pharmacological conditions are in good agreement with data from real rats.
-
the effects of pentylenetetrazol chlordiazepoxide and caffeine in rats tested in the Elevated Plus Maze depend on the experimental illumination
Behavioural Brain Research, 2011Co-Authors: Andrea Milena Becerra Garcia, Fernando P. Cardenas, Silvio MoratoAbstract:Abstract The so-called anxiolytic and anxiogenic drugs are considered to cause, respectively, increases and decreases in Plus-Maze open arm exploration, without modifying locomotor activity occurring in the closed arms in an Elevated Plus-Maze when the animals are tested in an illuminated environment. Simply testing animals in the dark also increases open arm exploration, which may be interpreted as an anxiolytic effect. We investigated the effects of two GABAergic drugs, pentylenetetrazol (10 and 20 mg/kg) and chlordiazepoxide (1.5 and 3 mg/kg), and one non-GABAergic drug, caffeine (10 and 30 mg/kg) on anxiety levels of rats tested in the Elevated Plus-Maze under two illumination conditions, light or dark. All animals explored more the open arms in the dark. In the light, pentylenetetrazol decreased open arm exploration while chlordiazepoxide had the opposite effect. Neither pentylenetetrazol nor chlordiazepoxide had any effect in the dark. Caffeine, increased open arms exploration in both illumination conditions. These results indicate that light triggers aversion, a response mediated by GABA since the GABAergic drugs, but not caffeine, were ineffective when the rats were tested in the dark.
-
characterization of the rat exploratory behavior in the Elevated Plus Maze with markov chains
Journal of Neuroscience Methods, 2010Co-Authors: Julian Tejada, Silvio Morato, Geraldine Goes Bosco, Antonio C RoqueAbstract:The Elevated Plus-Maze is an animal model of anxiety used to study the effect of different drugs on the behavior of the animal. It consists of a Plus-shaped Maze with two open and two closed arms Elevated 50 cm from the floor. The standard measures used to characterize exploratory behavior in the Elevated Plus-Maze are the time spent and the number of entries in the open arms. In this work, we use Markov chains to characterize the exploratory behavior of the rat in the Elevated Plus-Maze under three different conditions: normal and under the effects of anxiogenic and anxiolytic drugs. The spatial structure of the Elevated Plus-Maze is divided into squares, which are associated with states of a Markov chain. By counting the frequencies of transitions between states during 5-min sessions in the Elevated Plus-Maze, we constructed stochastic matrices for the three conditions studied. The stochastic matrices show specific patterns, which correspond to the observed behaviors of the rat under the three different conditions. For the control group, the stochastic matrix shows a clear preference for places in the closed arms. This preference is enhanced for the anxiogenic group. For the anxiolytic group, the stochastic matrix shows a pattern similar to a random walk. Our results suggest that Markov chains can be used together with the standard measures to characterize the rat behavior in the Elevated Plus-Maze.
-
prenatal stress produces more behavioral alterations than maternal separation in the Elevated Plus Maze and in the Elevated t Maze
Behavioural Brain Research, 2005Co-Authors: Celio Estanislau, Silvio MoratoAbstract:Prenatal stress and maternal separation are used in a large number of studies on early adversity consequences and present some similarities in their effects. The present work investigates the behavioral effects of these two procedures on two models of anxiety: the Elevated Plus-Maze and the Elevated T-Maze. During pregnancy, female rats were submitted to uncontrollable electric foot shock sessions every other day or kept undisturbed. After delivery, litters from undisturbed dams were submitted to either 180-min daily periods of maternal separations from the 3-14th postnatal days or maintained with the dams all the time. Litters from the stressed dams were left undisturbed from the 3-14th postnatal days. Only males were tested. In adulthood, rats were tested in the Elevated T-Maze or in the Elevated Plus-Maze. In the latter procedure half the subjects were submitted to a 60-min period of restraint immediately before being tested. The following measures were taken in the Elevated Plus-Maze: frequency and time spent in entries into the arms, stretching, rearing, grooming and head dipping. In the T-Maze measures of avoidance and escape latencies were used. Our data indicated that prenatal stress had more pronounced anxiogenic effects than maternal separation, as judged by reduced exploration of the open arms of the Elevated Plus-Maze, but mainly after the restraint stress, and increase in avoidance latencies in the Elevated T-Maze. The other measures not directly involved in the Elevated Plus-Maze arm exploration yielded similar results. Our data indicate that prenatal stress causes more anxiogenic effects in adulthood than maternal separation but, in the Elevated Plus-Maze, these anxiogenic effects are better seen immediately after an acute stress.
-
effects of apomorphine on rat behavior in the Elevated Plus Maze
Physiology & Behavior, 2005Co-Authors: Andrea Milena Becerra Garcia, Marcus Lira Brandão, Raquel Chacon Ruiz Martinez, Silvio MoratoAbstract:It has been reported that novelty may evoke both an exploratory and a fear drive, thus generating behavior responding to an approach/avoidance conflict. However, not much is known about the approach component. Whereas there exists abundant evidence referring to the avoidance component as the main target for the anxiolytic action of benzodiazepines, the involvement of dopaminergic mechanisms in fear and anxiety is controversial. The present study examined the effects of the dopaminergic agonist apomorphine, the D(2) dopaminergic antagonist sulpiride and the combined treatment sulpiride Plus apomorphine on conventional and non-conventional measures of the behavior of rats exposed to an Elevated Plus-Maze. Systemic injection of apomorphine (0.25, 0.5 and 1.0 mg/kg) caused a selective increase in the time spent in the open arms and in the open arm extremities. Pre-treatment with sulpiride blocked these effects while this dopaminergic antagonist had no effect by its own. Apomorphine produced no significant effects on stretching, flat-back-approach or scanning. Therefore, apomorphine increased the behavioral response linked to the approach component of the conflict without affecting risk assessment behaviors. These findings suggest that dopaminergic mechanisms, probably through D(2) receptors, may also be involved in the mediation of the conflict derived from the need of gathering information for confirming, identifying and localizing danger and take the appropriate action for avoiding the threatening stimuli of the Elevated Plus-Maze. A role for dopaminergic mechanisms in the setting up of adaptive responses in a fear-inducing environment is discussed.
Marcus Lira Brandão - One of the best experts on this subject based on the ideXlab platform.
-
exploratory behaviour of rats in the Elevated Plus Maze is differentially sensitive to inactivation of the basolateral and central amygdaloid nuclei
Brain Research Bulletin, 2007Co-Authors: Caio M Moreira, Marcus Lira Brandão, Sueli Masson, Milene C CarvalhoAbstract:The amygdala has a crucial role in detecting motivationally significant inputs and in communicating relevant information to other limbic structures. Behavioural studies have shown that the central (CeA) and basolateral (BLA) nuclei of amygdala differentially regulate conditioned and unconditioned fear. Indeed, much evidence has accumulated suggesting that regulatory mechanisms in the BLA serve as a filter for unconditioned and conditioned aversive information that ascends to higher structures from the brainstem, whereas the CeA is the main output for the autonomic and somatic components of fear reaction through major projections to other limbic regions. It is still unclear, however, how amygdaloid nuclei function in high and open spaces so as to determine the characteristic exploratory behaviour of rats submitted to the Elevated Plus-Maze test (EPM). In the present study, we carried out an ethopharmacological analysis of the behaviour of rats submitted to the Elevated Plus-Maze test together with analysis of the tissue content of monoamine dopamine (DA) and serotonin (5-HT) and their metabolites in the dorsal hippocampus (DH), nucleus accumbens (NAC) and dorsal striatum (DS) of animals injected with saline or muscimol (1.0 nmol/0.2 μL) into the BLA or CeA. The data obtained show that injections of muscimol into the CeA, but not into the BLA, caused anxiolytic-like effects in the EPM. Such effects of muscimol into the CeA were accompanied by increases in 5-HT content of the DH, whereas corresponding injections into the BLA caused a reduction in the DA content of the NAC. There was no change in the turnover rates of these monoamines. These data suggest that the BLA and CeA have distinct roles in the exploratory behaviour of rodents in the EPM. While BLA appears to be related to the detection and validation of threatening stimuli, the CeA appears to be involved in the expression of fear behaviours in the EPM.
-
effects of apomorphine on rat behavior in the Elevated Plus Maze
Physiology & Behavior, 2005Co-Authors: Andrea Milena Becerra Garcia, Marcus Lira Brandão, Raquel Chacon Ruiz Martinez, Silvio MoratoAbstract:It has been reported that novelty may evoke both an exploratory and a fear drive, thus generating behavior responding to an approach/avoidance conflict. However, not much is known about the approach component. Whereas there exists abundant evidence referring to the avoidance component as the main target for the anxiolytic action of benzodiazepines, the involvement of dopaminergic mechanisms in fear and anxiety is controversial. The present study examined the effects of the dopaminergic agonist apomorphine, the D(2) dopaminergic antagonist sulpiride and the combined treatment sulpiride Plus apomorphine on conventional and non-conventional measures of the behavior of rats exposed to an Elevated Plus-Maze. Systemic injection of apomorphine (0.25, 0.5 and 1.0 mg/kg) caused a selective increase in the time spent in the open arms and in the open arm extremities. Pre-treatment with sulpiride blocked these effects while this dopaminergic antagonist had no effect by its own. Apomorphine produced no significant effects on stretching, flat-back-approach or scanning. Therefore, apomorphine increased the behavioral response linked to the approach component of the conflict without affecting risk assessment behaviors. These findings suggest that dopaminergic mechanisms, probably through D(2) receptors, may also be involved in the mediation of the conflict derived from the need of gathering information for confirming, identifying and localizing danger and take the appropriate action for avoiding the threatening stimuli of the Elevated Plus-Maze. A role for dopaminergic mechanisms in the setting up of adaptive responses in a fear-inducing environment is discussed.
-
Acute and chronic effects of gepirone and fluoxetine in rats tested in the Elevated Plus-Maze: an ethological analysis.
Pharmacology biochemistry and behavior, 2000Co-Authors: R.c.b. Silva, Marcus Lira BrandãoAbstract:The potential role of 5-hydroxytryptamine (5-HT) in anxiety has been the subject of much research, most of it addressed to the hypothesis that 5-HT promotes anxiety and, therefore, that drugs that reduce 5-HT functions will be effective anxiolytic agents in human anxiety disorders. However, the effects of serotoninergic drugs in different behavioral paradigms have been inconsistent. These inconsistencies have been particularly well illustrated in the Elevated Plus-Maze. In the present study we provided an ethopharmacological analysis (in addition to conventional measures) of the behavior of rats in the Elevated Plus-Maze with transparent walls after acute and chronic treatments with gepirone, an agonist of 5-HT1A receptors, and fluoxetine, a selective inhibitor of serotonin reuptake. Although gepirone has been used to treat anxiety, fluoxetine is a mainstay in the treatment of depression. Acute treatment with gepirone (1, 3, 5.6, and 10 mg/kg, IP) produced an anxiogenic profile with increased risk assessment behaviors (e.g., flat-back approach) and decreased behavioral measures that are inversely related to “anxiety” (e.g., head dipping and end-arm activity). In contrast, chronic gepirone (10 mg/kg day, PO) produced an opposite effect showing an anxiolytic profile that is consistent with the clinical use of this drug, which shows efficacy after 2–4 weeks of treatment. Acute fluoxetine (5.6 and 10 mg/kg, IP) also produced an anxiogenic profile with reduced head dipping and end-arm activity. On the other hand, chronic fluoxetine (10 mg/kg day, PO) had no effect on any of the behavioral measures. These data demonstrate: (a) the anxiogenic and anxiolytic effects of acute and chronic gepirone, respectively, corroborate with the observed effects of these treatments in the clinic; (b) similarly, the anxiogenic effects of acute fluoxetine observed here have also been reported in clinical studies with 5-HT reuptake blockers. This class of compounds has not been systematically used as anxiolytic; (c) the Elevated Plus-Maze with transparent walls shows good sensitivity for evaluating serotonergic drugs with anxiogenic and anxiolytic profile.
Catherine Belzung - One of the best experts on this subject based on the ideXlab platform.
-
correlations between behaviours in the Elevated Plus Maze and sensitivity to unpredictable subchronic mild stress evidence from inbred strains of mice
Behavioural Brain Research, 2005Co-Authors: C Ducottet, Catherine BelzungAbstract:This study aimed at investigating the relationship between anxiety-like and depressive-like behaviour in mice. Therefore, we assessed the behaviour of mice from eight different strains (FVB/NA, BALB/c, C57BL/6, DBA/2, 129/Sv, C3H/He, CBA and BA) confronted first to anxiety models (the Elevated Plus-Maze and the free exploratory test) and then to tests of depressive-like behaviours (forced swim test and unpredictable subchronic mild stress). In the forced swim test, mice from the DBA/2, the BA and the C3H/He strains displayed higher immobility than mice from the 129/Sv, the BALB/c, the C57BL/6 and the CBA strains. In the subchronic mild stress, mice from the C57BL/6 and the CBA strains displayed low sensitivity when compared with mice from all the others strains. A stepwise multiple regression analysis suggests that behaviour in the Elevated Plus-Maze is associated with the time of immobility in the forced swim test (20%) and with the susceptibility to the unpredictable subchronic stress procedure (31%). The behaviour in the free exploratory paradigm is slightly associated with behaviours in the two tests of depression. These results suggest that anxiety may be a factor contributing, among others, to the susceptibility to depressive-like behaviours.
-
behaviour in the Elevated Plus Maze predicts coping after subchronic mild stress in mice
Physiology & Behavior, 2004Co-Authors: C Ducottet, Catherine BelzungAbstract:This study was aimed at investigating the coping style of mice subjected to a subchronic unpredictable mild stress procedure and its relationship to initial emotional reactivity. Two inbred strains of mice, the BALB/c ByJ and the C57BL/6 J, known to exhibit distinct emotionality, have been used. They were first observed in the Elevated Plus-Maze and the free exploratory paradigm, each provides a separation of the population in high and low emotional mice. Half of the mice of each strain were then confronted to a 2-week subchronic unpredictable mild stress and tested for their responses in different behavioural situations (consumption of a palatable food, physical state, grooming behaviours and reactivity to a conflict situation). Mice were also tested in the light/dark procedure to assess the effect of the subchronic stress on emotional reactivity. First, a relationship between initial emotional reactivity in the Elevated Plus-Maze and behavioural coping style in response to stress was found, high emotional mice (i.e., BALB mice) displaying inhibited behaviours and less emotional mice (i.e., BL/6 mice) exhibiting few behavioural changes. Furthermore, emotional reactivity was increased in stressed mice compared with nonstressed ones.
Michel Bourin - One of the best experts on this subject based on the ideXlab platform.
-
effects of acute fluoxetine paroxetine and desipramine on rats tested on the Elevated Plus Maze
Behavioural Brain Research, 2007Co-Authors: Dominique Drapier, Michel Bourin, Daniele Bentueferrer, Bruno Laviolle, Bruno Millet, Herve Allain, J M ReymannAbstract:Antidepressants are usually prescribed for the treatment of depression but more recently have also been recommended for the treatment of anxiety disorders. The purpose of this study was to investigate the anxiogenic- or anxiolytic-like effects of an acute administration of antidepressants (serotonergic and noradrenergic compounds) in male Wistar rats submitted to the Elevated Plus-Maze. Fluoxetine (2.5, 5, 10, 15 mg/kg), paroxetine (0.1, 0.5, 3, 12 mg/kg) and desipramine (2.5, 5, 10 mg/kg) or their vehicles were administered intraperitoneally 30 min prior to testing. Diazepam (0.5, 1.5, 2.5 mg/kg) was used as a positive comparator for anxiolytic effect. In comparison with control animals, the percentage of time the rats treated with fluoxetine (5 and 10 mg/kg) and paroxetine (3 and 12 mg/kg) spent in the open arms decreased. The percent of inactive time spent in the open arms also decreased in rats given fluoxetine (5 and 10 mg/kg) and paroxetine (12 mg/kg). Desipramine was inactive on all these parameters. In conclusion, acute treatment with fluoxetine and paroxetine, but not with desipramine, produced a pattern of anxiety behavior. Thus, the pharmacological mechanism appears to be due more to serotonergic than adrenergic neurotransmission. The Elevated Plus-Maze exhibits good sensitivity for detecting anxiogenic effects of antidepressant drugs and the conventional parameters are sufficient and reliable for detecting such effects.
-
light dark cycle manipulation influences mice behaviour in the Elevated Plus Maze
Behavioural Brain Research, 2006Co-Authors: Florence Clenet, Martine Hascoet, Eric Bouyon, Michel BourinAbstract:The sensitization of animal models of anxiety is of great importance to detect potential anxiolytic drugs. Our goal was to evaluate the influence of manipulations of the light/dark cycle on the basal anxious behaviour of mice and the efficacy of two anxiolytic treatments in the mouse Elevated Plus Maze (EPM). Male Swiss mice were exposed to different conditions of illumination for one week prior to testing. In the first experiment of the study, we evaluated the anxiolytic effects of diazepam, at the dose of 1 mg/kg, intraperitoneally (i.p.) administered 30 min before the test. In the second experiment, we examined the effects of WAY 100635, a 5-HT(1A) receptor antagonist, at the doses of 0.03 and 2 mg/kg, i.p. administered 30 min before the test. The locomotor activity of control mice and the anxiolytic efficacy of diazepam in the EPM were not affected by manipulation of the light/dark cycle. Conversely, the effects of WAY 100635, which were qualitatively different from those of diazepam, seemed to be influenced by the illumination conditions imposed before the test. We can conclude that diazepam's effect, which is characterized by a strong "disinhibition", was more robust than the 5-HT(1A) antagonist's effect, which was more anxioselective. Moreover, the light conditions imposed on mice before the test may be an important factor in the variability of the response to serotonergic but not to benzodiazepine treatments.
-
role of gaba ergic and serotonergic systems in the anxiolytic like mechanism of action of a 5 ht moduline antagonist in the mouse Elevated Plus Maze
Behavioural Brain Research, 2005Co-Authors: Florence Clenet, Martine Hascoet, G Fillion, Herve Galons, Michel BourinAbstract:5-HT-moduline is an endogenous tetrapeptide, which acts specifically as an antagonist of 5-HT1B auto- and heteroreceptors. HG1 is an ethyl arylmethyloxypiperidine acetate and an antagonist of 5-HT-moduline, which has no 5-HT-moduline agonist effect. In a pilot study, HG1 has demonstrated an anxiolytic-like profile in three mouse models of anxiety (Elevated Plus Maze, light/dark, four plates). The aim of our study was to examine the mechanism of the anxiolytic-like effects of HG1 in the mouse Elevated Plus Maze. Male Swiss mice were acutely administered HG1 at active doses in association with GABA antagonists such as fluMazenil, bicuculline and picrotoxine, then, with 5-HT1A (NAN 190, WAY 100635) and 5-HT1B receptor antagonist (methiothepine). Finally, we tried to potentiate non-active doses of HG1 with 5-HT1A (8-OHDPAT) and 5-HT1B receptor agonists (anpirtoline) in the mouse Elevated Plus Maze. Regarding GABA antagonists, only fluMazenil antagonised active doses of HG1 in an incomplete manner. Moreover, non-active doses of HG1 were potentiated by low doses of WAY 100635 and by anpirtoline but not by 8-OHDPAT. Finally, the anxiolytic-like effects of HG1 at active doses were antagonised by all serotonergic antagonists (WAY 100635 at higher dose, NAN 190 and methiothepin). HG1 mechanism of action in the mouse Elevated Plus Maze seems to associate a GABA-ergic component exerting a limited regulation of 5-HT neuronal activity and a major serotonergic component, which seems to implicate presynaptic 5-HT1A and 5-HT1B receptors.