Elevated Plus-maze Test In Rats Research Articles

Comparative analysis of rats’ behavior in the «elevated plus maze» after the intranasal administration of single-walled carbon nanotubes in a small dose in subacute experiments of different duration

The unique properties of carbon nanotubes (CNT) (increased strength, flexibility, electrical and thermal conductivity) make them very promising for use in various fields of human activity. But the question of their toxic effects on the body is actively discussed in the literature. There is a lot of body toxicity data of large doses of CNT, but the question of the potential danger of small doses of CNT is a practically unexplored issue. Earlier, we showed that a single intranasal injection of single-walled CNT (SWCNT) in a small dose (4 μg / kg) to rats inhibited the mRNA production of most cytokines in both spleen and brain. At the same time, the expression of the early c-fos gene in the olfactory bulb and the pyriform cortex was increased [Loseva E.V. et al., 2016]. It is known very little about the effect of low doses of SWCNT on animal behavior. The aim of this study was to investigate the effect of a small doses of SWCNT with subacute intranasal administration of different duration on the behavior of rats in the elevated plus-maze (EPM) test, which is used to estimate the anxiety. Male Wistar rats were daily intranasal administrated 100 μl of SWCNT suspensions in physiological saline (PS) in small (5.2 μg / kg, n = 9) dose for 4 (n = 9) or 13 (n = 9) days. Control rats were administrated analogically 100 μl of PS (n = 19). A statistical analysis of indicators of rats' behavior in EPM (5 minutes each) was performed using Kruskal-Wallis one-way analysis of variance, and then using the comparison on the non-parametric criterion of Mann-Whitney for independent features by the program STATISTICA 7.0. It was shown that in the EPM test in rats after 4-fold injection of a small dose of SWCNT, as compared with the control group, there was observed the behavior activation in the center and open arm, what was expressed in frequent and lengthy visits, but with a reduction of the average time of such visits. These animals also had increased the vertical exploratory activity (rears), horizontal exploratory activity (head dips) and motor activity, but the grooming indicators were decreased. After chronic administration of SWCNT in a small dose for 13 days, the direction of some of these changes was maintained, but was expressed to a much lesser degree (only at the level of the tendency in comparison to the control group). So, these rats, compared with the control, more often and longer visited the central site, more often visited open arms and less time were in closed arms. At the same time, the average time of the dark visits was smaller, and the average time of grooming, on the contrary, was longer than in the control. Thus, the intranasal administration of SWCNT in a small dose for 4 days in rats had provoked atypical symptoms of anxiety, which were expressed in an agitated behavior in the EPM, as evidenced by the strong activation of most behavioral reactions. The intranasal administration of SWCNT in a small dose for 13 days also has led to some activation of behavior or atypical anxiety, but it was expressed to a much lesser extent than with the acute injection of SWCNT. There wasn't observed an increasing of agitated behavior or a cumulative negative effect of SWCNT during chronic intranasal injection. We can suggest that nanotubes when administered in a small dose for 4 days can penetrate cells and their organelles, causing damage and death of tissue structures, in particular, when they penetrate into the brain, which leads to agitated behavior. At the same time, with subacute administration of SWCNT in a small dose during 13 days, protective reactions can gradually develop, leading to accelerated utilization of nanotubes, for example, by macrophages and astrocytes, which can absorb them, that leads to a diminution of the activation of behavior. To test this assumption, special morpho-functional studies are required.

Effects in rats of adolescent exposure to Cannabis sativa on emotional behavior and adipose tissue.

Cannabis sativa L has remained the most widely used recreational and abused drug worldwide. This study determined adipose tissue histological changes and the anxiety-like behavior in elevated plus-maze tests in rats treated with C. sativa. C. sativa L. was provided from Islamic Azad University Herbarium. To reach cannabis powder, a rotary evaporator was used. Forty-five male Wistar rats were randomly divided into three equal groups of experimental receiving 2 mg/kg of cannabis extract dissolved in 70 % ethanol in 0.6 mL volume subcutaneously daily for three weeks, the sham group subcutaneously injected with equal volume of 70 % ethanol and the control receiving just distilled water, identically. To assess the anxiety level, elevated plus maze was used. Histopathological changes in adipose tissue was evaluated after 7, 14, and 21 days post-intervention. After cannabis administration, inflammation, degeneration and necrosis in adipose tissue occured. Regarding the anxiety level for the percentage of time spent in open arm (OAT), the percentage of time spent in closed arm (CAT), the percentage of time spent in central parts, and head dipping over the side of the maze) after one week, no significant difference was noticed between the groups; but 2 and 3 weeks of cannabis use, the anxiety level significantly increased. Histological findings denoted to inflammation, degeneration and necrosis in adipose tissue after cannabis use. Behavioral assessment of anxiety level revealed that one week after cannabis, no changes were seen in anxiety, but 2 and 3 weeks after cannabis use, the anxiety level increased significantly (Fig. 5, Ref. 38).

Time-of-Day and Age Impact on Memory in Elevated Plus-Maze Test in Rats.

The purpose of the present study was to establish the effect of daytime and aging on memory in rats in the Elevated Plus-Maze (EPM) test. Young (2-months) and aged (18-months) male Wistar rats were exposed to the EPM test, at the beginning, mid-time or at the end of the light period. On the acquisition trial, the animals were placed individually at the end of one of the open arms of the EPM and the latency to enter in the enclosed arms was registered (cut-off time 60 s). The test was repeated 24 h later on. A longer latency period to reach the enclosed arm indicated poor retention compared to significantly shorter latencies. There were no significant differences between groups on the acquisition trial. In all tested periods, the latency time on the 24 h retention trial was significantly shorter in the young rats compared to the old ones. Furthermore, in the early and mid-time period of the light period, the young rats showed significantly decreased transfer latency (TL) time on the 24 h retention trial in comparison with the acquisition trial. In the aged rats, the TL time on the 24 h retention trial was significantly longer at the end of the light period, in comparison to the two other testing periods. In conclusion, aging significantly affects memory and the more critical period for memory process in both young and old animals, particularly at the end of the light period of the circadian cycle.

EXPERIMENTAL EVALUATION OF ANTIDEPRESSANT AND ANTIANXIETY ACTIVITIES OF AQUEOUS LEAF EXTRACTS OF SENNA ALATA (L.) ROXB. USING IN VITRO ANIMAL MODELS

Objective: In the present investigation antidepressant and antianxiety activities of aqueous leaf extracts of Senna alata (200 mg/Kg) were carried out to establish the species as a potent natural antidepressant and anxiolytic drug.Methods: Antidepressant activity was carried out using forced swim test and tail suspension test. In both these tests, the animals were subjected to external stress that results in alteration of the behavior of animal due to fear.The antianxiety activity of aqueous leaf extracts of S. alata has been studied by the elevated plus-maze test in rats. The mean number of entries and the time spent in the open arm after 45 min of the administration of test drug was noted to determine the antianxiety effect of the test drug.Results: For antidepressant activity administration of test drug (200 mg/Kg) showed a significant decrease in the time spent by the animal in state of depression in both the assays which clearly indicates that the aqueous leaf extracts of S. alata exhibited a strong antidepressant activity similar to that of the control drug (Imipramine).In the antianxiety activity, administration of aqueous leaf extract (200 mg/Kg) of S. alata significantly increased the mean number of entries (2.25±0.98) in the open arm and the time spent in open arm (2.23±0.04) compared to the control group. The activity of the extract was slightly greater than standard drug Diazepam.Conclusion: From the above-presented results, it can be concluded that administration of Senna alata aqueous leaf extracts (200 mg/Kg) showed a considerable decrease in both antidepressant and antianxiety activities in all the test animals and can be used in the replacement of commercially available synthetic drugs in the near future.

Beneficial effects of ellagic acid against animal models of scopolamine- and diazepam-induced cognitive impairments

Context In a previous study, it has been shown that ellagic acid (EA), a polyphenolic compound found in pomegranate and different berries, prevents cognitive and hippocampal long-term potentiation (LTP) impairments induced by traumatic brain injury in rats through antioxidant and anti-inflammatory mechanisms.Objective The present study was conducted to assess the potential of EA as a memory enhancer.Materials and methods The elevated plus maze (EPM) and passive avoidance (PA) paradigm were used to evaluate learning and memory parameters. Three doses (10, 30 and 100 mg/kg, i.p.) of EA were administered to animals. Memory impairment was induced by scopolamine treatment (0.4 mg/kg, i.p.) and/or diazepam (1 mg/kg, i.p.). Acquisition trials were carried out 30 min after scopolamine treatment and retention trials were performed for 5 min 24 h after the acquisition trials.Results EA at doses 30 and 100 mg/kg significantly reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) in the EPM and PA tests in mice. Also, EA at doses 30 and 100 mg/kg significantly antagonized the amnesia induced by diazepam (1 mg/kg, i.p.) in EPM test in rats. Moreover, chronic administration of EA at dose 30 mg/kg ameliorated the memory deficit induced by diazepam (1 mg/kg, i.p.) in rats.Discussion and conclusion This study demonstrates that ellagic acid is effective in preventing scopolamine- and diazepam-induced cognitive impairments without altering the animals’ locomotion. This suggests the potential of EA application as a useful memory restorative agent in the treatment of dementia seen in elderly persons.

Effects of combined ferrous sulfate administration and exposure to static magnetic field on brain oxidative stress and emotional behavior.

The present study was done to investigate behavioral effects and oxidative stress in iron- treated and co-exposed static magnetic field (SMF)-iron rats. Anxiety in the elevated plus- maze test, and motor skills were also assessed in the stationary beam and suspended string tests. After behavioral tests, the rats were anesthetized and their brains were removed for biochemical analysis. The co-exposure to iron and SMF induced a significant difference in elevated plus-maze test in rats. The frequency of entries and time spent in the open arms was significantly reduced (p<0.05) in the iron- and SMF-exposed group compared with the group treated with iron alone and in the control group. However, no significant difference was noticed for the motor skill test between the three groups. The biochemical investigation showed that malondialdehyde level increased (p<0.001) and that glutathione level and catalase enzyme activity decreased (p<0.001) in brain of iron- and SMF-exposed group. The dose of iron alone used in present study, was unable to induce any effect. However, the 128 mT SMF in the presence of iron ions in the body can induce disruption in the emotional behavior and can produce oxidative stress in brain tissue of rats.

Effects of combined ferrous sulfate administration and exposure to static magnetic field on brain oxidative stress and emotional behavior

The present study was done to investigate behavioral effects and oxidative stress in iron- treated and co-exposed static magnetic field (SMF)–iron rats. Anxiety in the elevated plus- maze test, and motor skills were also assessed in the stationary beam and suspended string tests. After behavioral tests, the rats were anesthetized and their brains were removed for biochemical analysis. The co-exposure to iron and SMF induced a significant difference in elevated plus-maze test in rats. The frequency of entries and time spent in the open arms was significantly reduced (p&lt;0.05) in the iron- and SMF-exposed group compared with the group treated with iron alone and in the control group. However, no significant difference was noticed for the motor skill test between the three groups. The biochemical investigation showed that malondialdehyde level increased (p&lt;0.001) and that glutathione level and catalase enzyme activity decreased (p&lt;0.001) in brain of iron- and SMF-exposed group. The dose of iron alone used in present study, was unable to induce any effect. However, the 128 mT SMF in the presence of iron ions in the body can induce disruption in the emotional behavior and can produce oxidative stress in brain tissue of rats.

Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats

The effects of mitragynine on anxiety-related behaviours in the open-field and elevated plus-maze tests were evaluated. Male Sprague-Dawley rats were orally treated with mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) 60 min before behavioural testing. Mitragynine doses used in this study were selected on the basis of approximately human equivalent doses with reference to our previous literature reports. Acute administration of mitragynine (10, 20 and 40 mg/kg) or diazepam (10 mg/kg) increased central zone and open arms exploration in the open-field and elevated plus-maze tests respectively. These anxiolytic-like effects of mitragynine were effectively antagonized by intraperitoneal administration of naloxone (2 mg/kg), flumazenil (10 mg/kg), sulpiride (0.5 mg/kg) or SCH 23390 (0.02 mg/kg) 15 min before mitragynine treatments. These findings reveal that the acute administration of mitragynine produces anxiolytic-like effects and this could be possibly attributed to the interactions among opioidergic, GABAergic and dopaminergic systems in brain regions involved in anxiety.

The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats

Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy.

Effects of serotonergic terminal lesion in the amygdala on conditioned fear and innate fear in rats

The amygdala and the medial prefrontal cortex (mPFC) are crucial brain structures for anxiety, and it is speculated that the serotonergic neural system in these structures has an important role in regulating anxiety. In our previous study, we indicated that local injections of selective serotonin reuptake inhibitor into the amygdala attenuated anxiety-related behaviors in conditioned fear in rats. In the present study, we investigated the effects of serotonergic terminal lesions in the amygdala and in mPFC induced by local injection of 5,7-dihydroxytryptamine (5,7-DHT), on anxiety-related behaviors in conditioned fear and the elevated plus-maze test in rats. A 5,7-DHT lesion in the amygdala attenuated memory-dependent fear assessed by conditioned fear, but enhanced memory-independent fear assessed by the elevated plus-maze test. These results suggest that the role of the amygdalar serotonergic system in fear is different between memory-dependent and independent fear and, in particular, it is paradoxical that an amygdalar serotonergic lesion exerts a similar effect on memory-dependent fear to SSRI. Moreover, a serotonergic lesion in the amygdala enhanced the retrieval of extinction memory in conditioned fear; however, a serotonergic lesion in mPFC did not bring about any behavioral changes.

Anxiolytic-like effects of olanzapine, risperidone and fluoxetine in the elevated plus-maze test in rats

In the present study was examined the effect of treatment with olanzapine or risperidone, given separately or in combination with fluoxetine, in the elevated plus-maze test (an animal model of anxiety) in male Wistar rats. The obtained results showed that treatment with olanzapine (1mg/kg), risperidone (0.1 and 0.3mg/kg) or fluoxetine (5 and 10mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test. Olanzapine, risperidone and fluoxetine, tested in doses effective in the model of anxiolytic-like actions, did not affect motor coordination, while olanzapine (3mg/kg) and risperidone (0.3mg/kg) produced a significant reduction of exploratory activity in the open field test. In a combination study, the anxiolytic-like effect of olanzapine or risperidone was significantly antagonized by co-treatment with fluoxetine. Additionally, co-treatment with olanzapine or risperidone and fluoxetine disturbed the motor coordination of rats in a rota-rod test. These findings indicate that olanzapine, risperidone and fluoxetine per se may be clinically effective in treating anxiety disorders, but their effects may be attenuated when they are used in combination with other medications.

Assessment of amphetamine withdrawal anxiety-like behavior in the elevated plus-maze test in rats

Assessment of amphetamine withdrawal anxiety-like behavior in the elevated plus-maze test in rats

Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAA receptor expression, and behavioral sensitivity to anxiolytic drugs

Gonadal steroids, in particular estradiol, exert important actions during pre- and perinatal periods in the regulation of sexual dimorphism and development of the nervous system. We have now examined the effects of neonatal estradiol administration in female rats on brain concentrations of the neuroactive steroids allopregnanolone and tetrahydrodeoxycorticosterone, expression of GABA(A) receptor subunits, and behavioral sensitivity to benzodiazepines and allopregnanolone. Administration of beta-estradiol 3-benzoate on the day of birth resulted in marked decreases in the concentrations of progesterone and allopregnanolone in the cerebral cortex at 21, 60, and 180 days after birth. The concentrations of tetrahydrodeoxycorticosterone, 17beta-estradiol, and dehydroepiandrosterone in the brain at 60 days were not affected by such treatment. Neonatal administration of beta-estradiol 3-benzoate also increased the cerebrocortical abundance of alpha(1), alpha(2), and gamma(2) subunits of the GABA(A) receptor without affecting that of alpha(3), alpha(4), alpha(5), or delta subunits. Diazepam induced a greater reduction in locomotor activity as well as a more pronounced anxiolytic-like effect in the elevated plus-maze test in rats subjected to neonatal treatment with beta-estradiol 3-benzoate than in vehicle-treated controls, while allopregnanolone induced a similar effect in both groups. These effects of estradiol suggest that it plays a major role in regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system.

MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences

Event Abstract Back to Event MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences Shih Chun Ho1* and Ying Jui Ho1 1 Chung Shan Medical University, School of Psychology, Taiwan Animals treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are used as models of Parkinson's disease. This study analyzed changes of motor, anxiety, recognition, and learning in MPTP-lesioned Wistar rats and C57BL/6 mice, which was intended to establish a useful model of Parkinson's disease dementia. MPTP was bilaterally infused into the substantia nigra pars compacta (SNc) of male Wistar rats. Starting one day after the MPTP lesion, the rats were subjected to a battery of behavioral tests for measuring motor function in the rotarod, anxiety level in the elevated plus-maze (EPM), learning and working memory in the T-maze, and recognition in the object recognition task. Male C57BL/6 mice receiving intraperitoneal injection of MPTP were subjected to a battery of behavioral tests for measuring motor function in the open field, anxiety level in the EPM, learning function in the active avoidance task (AAT), and recognition in the object recognition task. Both rats and mice showed motor deficits in the rotarod and open field test, respectively, one day after MPTP lesioning. However, such impairments in the rats were reversed to control levels 7 days after the MPTP lesion, which were assessed by measuring percentage of movement time on the rotarod. Similarly, analyzing total distance and movement time in the open field, motor impairments of the mice were also reversed to control levels 11 days after the MPTP lesion. Decreased exploration time to novel objects in the object recognition test was observed in both rats and mice treated by MPTP. MPTP lesion suppressed open arm time and open arm entry in the EPM test in rats, but not in mice. In addition, MPTP-lesioned rats showed lowered correct responses in the T-maze test. However, no effect of MPTP lesion was found on learning ability in the AAT in mice. In summary, MPTP lesion in rats caused deficits in motor, anxiety, recognition, and learning ability. MPTP-treated mice showed impairments in movement and recognition, but not in anxiety level and learning ability. These results provide evidence for taking the species differences into account when animal models for studying symptoms of early phase of Parkinson's disease dementia. Keywords: Parkinson's disease dementia ; MPTP ; Species differences ; Motor function ; Anxiety level ; Learning ; Recognition ; Animal model Conference: Neuroinformatics 2010 , Kobe, Japan, 30 Aug - 1 Sep, 2010. Presentation Type: Poster Presentation Topic: Clinical neuroscience Citation: Chun Ho S and Jui Ho Y (2010). MPTP-induced Animal Model of Parkinson's Disease Dementia: There are Species Differences. Front. Neurosci. Conference Abstract: Neuroinformatics 2010 . doi: 10.3389/conf.fnins.2010.13.00094 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 14 Jun 2010; Published Online: 14 Jun 2010. * Correspondence: Shih Chun Ho, Chung Shan Medical University, School of Psychology, Taichung, Taiwan, gorgeous-1023@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Shih Chun Ho Ying Jui Ho Google Shih Chun Ho Ying Jui Ho Google Scholar Shih Chun Ho Ying Jui Ho PubMed Shih Chun Ho Ying Jui Ho Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Dansyl-PQRamide, a putative antagonist of NPFF receptors, reduces anxiety-like behavior of ethanol withdrawal in a plus-maze test in rats

Much evidence indicates that endogenous opioid peptides are involved in effects caused by ethanol. The aim of the present study was to determine whether dansyl-PQR amide, a putative antagonist of receptors for an anti-opioid peptide—neuropeptide FF (NPFF) could affect anxiety-like behavior measured during withdrawal from acute-, and chronic ethanol administration in the elevated plus maze test in rats. Our study indicated that intracerebroventricular (i.c.v.) administration of dansyl-PQRamide (2.4 and 4.8 nmol) reversed anxiety-like behavior measured as a percent time spent in the open arms, and a percent open arm entries onto the open arms in the elevated plus-maze test in rats. These effects were inhibited by NPFF (10 and/or 20 nmol, i.c.v.) in the experiments performed during withdrawal from acute- and chronic ethanol administration. During withdrawal from acute ethanol, naloxone (1 mg/kg, i.p.), a nonselective opioid receptor antagonist, attenuated only an increased percent time spent in the open arms induced by dansyl-PQR amide (4.8 nmol). Dansyl-PQR amide, NPFF and naloxone given alone to naive rats did not have influence on spontaneous locomotor activity of animals. Furthermore, NPFF potentiated anxiety-like behavior during withdrawal from chronic, but not acute, ethanol administration in rats. Our data suggest that NPFF system is involved in regulation of affective symptoms of ethanol withdrawal. It seems that involvement of the NPFF system in ethanol withdrawal anxiety-like behavior is associated with regulation of the opioid system activity.

The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats

The aim of the present study was to determine whether various glutamate receptor antagonists could affect ethanol withdrawal-induced anxiety-like behavior measured in the elevated plus-maze test in rats. In our study, memantine (8 and 12 mg/kg), a noncompetitive N-methyl- d-aspartate (NMDA) receptor antagonist, did not show any effect on ethanol withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate5 (mGlu5) receptor antagonist), at a dose of 400 mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and open arms entries. Antagonists of group I mGlu receptors, such as MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, mGlu5 receptor) or EMQMCM (3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate, mGlu1 receptor), caused similar effects to acamprosate. In contrast to acamprosate and MTEP, EMQMCM (5 mg/kg) elevated the ethanol withdrawal-induced decrease in locomotion. When given alone to the saline-treated group, EMQMCM indicated anxiolytic-like effect. Our results imply a crucial role of mGlu5 receptor in an anxiety-like effect of ethanol withdrawal because MTEP (a selective mGlu5 receptor antagonist) and acamprosate (which also indirectly inhibits mGlu5 receptor) attenuated ethanol withdrawal anxiety-like behavior without influence on ethanol withdrawal hypolocomotion and did not show any effect in the saline-treated groups. However, difference in anxiolytic-like potency between both these group I mGlu receptors antagonists may be due to the recent experimental design. Therefore, taking into account a positive correlation between ethanol withdrawal-induced anxiety and relapse to ethanol drinking, our results suggest that mGlu receptor antagonists of group I (similarly to acamprosate) could prevent relapse to drinking and, therefore they might be useful in therapy of alcoholism.

Effects of the brain-penetrant and selective 5-HT6 receptor antagonist SB-399885 in animal models of anxiety and depression

The effects of a selective 5-HT6 receptor antagonist, SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide), were evaluated in behavioural tests sensitive to clinically effective anxiolytic- and antidepressant-compounds using diazepam and imipramine as reference drugs. In the Vogel conflict drinking test in rats, SB-399885 (1–3mg/kg i.p.) caused an anxiolytic-like activity comparable to that of diazepam (2.5–5mg/kg i.p.). An anxiolytic-like effect was also seen in the elevated plus-maze test in rats, where SB-399885 (0.3–3mg/kg i.p.) was slightly weaker than diazepam (2.5–5mg/kg i.p.). In the four-plate test in mice, SB-399885 (3–20mg/kg i.p.) showed an anxiolytic-like effect which was weaker than that produced by diazepam (2.5–5mg/kg i.p.). In the forced swim test in rats, SB-399885 (10mg/kg i.p.) significantly shortened the immobility time and the effect was stronger than that of imipramine (30mg/kg i.p.). In the forced swim test in mice, SB-399885 (20–30mg/kg i.p.) had an anti-immobility action, comparable to imipramine (30mg/kg i.p.) and also in the tail suspension test in mice, SB-399885 (10–30mg/kg i.p.) had an antidepressant-like effect, though was weaker than imipramine (10–20mg/kg i.p.). The tested 5-HT6 antagonist (3-20mg/kg i.p.) shortened the walking time of rats in the open field test and, at a dose of 30mg/kg i.p. reduced the locomotor activity of mice. SB-399885 (in doses up to 30mg/kg i.p.) did not affect motor coordination in mice and rats tested in the rota-rod test. Such data indicate that the selective 5-HT6 receptor antagonist SB-399885had specific effects, indicative of this compound's anxiolytic and antidepressant potential.

Effect of the selective 5-HT 7 receptor antagonist SB 269970 in animal models of anxiety and depression

The aim of the present study was to examine the effect of the selective 5-HT 7 receptor antagonist SB 269970 (0.25–20 mg/kg) in the behavioral tests commonly used for predicting anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as standard drugs. SB 269970 (in one medium dose of 0.5 or 1 mg/kg) exerted a specific antianxiety-like effect in the Vogel drinking test in rats, in the elevated plus-maze test in rats and in the four-plate test in mice. Moreover, SB 269970 (in one medium dose of 5 or 10 mg/kg) showed antidepressant-like activity in the forced swimming and the tail suspension tests in mice. At the same time, the tested compound at doses of 1–20 mg/kg did not change the spontaneous locomotor activity of mice. The potential anxiolytic and antidepressant effects produced by SB 269970 were weaker than those of the reference drugs employed. It is noteworthy that the active doses of SB 269970 were devoid of any visible motor side-effects. In conclusion, the results of our studies indicate that 5-HT 7 receptor antagonists may play a role in the therapy of both anxiety and depression.

Synthesis, conformation analysis, and anxiolytic activity of retropeptide analogs of 4-cholecystokinin

Potential dipeptide anxiolytics with the general formula Ph(CH2)5 CO-X-L-Trp-NH2(X = Gly, β-Ala, GABA, L-Pro) have been synthesized on the basis of the 4-cholecystokinin structure. These compounds exhibit anxiolytic activity in the elevated plus-maze test in rats at doses of 0.01–0.5 mg/kg (i.p.). The activity among these derivatives increases in the following order: GABA → β-Ala → Gly → Pro. Conformation analysis of dipeptides in solution by 1H NMR method with the use of the nuclear Overhauser effect and peptide vicinal 3J(H-NCα-H) coupling constants has been carried out. It is established that the percentage of βI-turn conformation stabilized by hydrogen bonds with the participation of C-end amide group proton also increases in the order β-Ala → Gly → Pro derivatives. It is concluded that the βI-turn conformation is probably the biologically active one in the synthesized substituted dipeptides.

Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats

This study describes the effects of intra-lateral septal infusions of different doses of the mGluR5 antagonist MTEP in the DRL-72 s paradigm and the elevated plus-maze test in rats, two behavioral models known to be sensitive to antidepressant-like and anxiolytic-like drug effects, respectively. Intra-lateral septal infusions of MTEP induced a dose-dependent (5.0 μg/μl, P < 0.05; 10.0 μg/μl, P < 0.05) increase in reinforced lever presses and a cohesive rightward shift of the inter-response time distribution (5.0 μg/μl, P < 0.05; 10.0 μg/μl, P < 0.05). These effects are indicative of antidepressant-like actions of the compound. Desipramine, a prototypical antidepressant drug, induced (5.0 μg/μl; P < 0.05) similar effects. In the elevated plus-maze test, intra-lateral septal infusions of MTEP (5.0 μg/μl, P < 0.05; 10.0 μg/μl, P < 0.05) increased the exploration of the open arms without affecting locomotion. This anxiolytic-like effect was similar to that observed with the infusion of the benzodiazepine midazolam (10.0 μg/μl; P < 0.05) in the same brain area. It is concluded that intra-lateral septal infusions of the mGlu5 receptor antagonist MTEP produced antidepressant-like actions or anxiolytic-like effects in male rats.