Arm Entries Research Articles

Enhancing Spatial Memory: Anxiolytic and Antidepressant Effects ofTapinanthus dodoneifolius(DC) Danser in Mice

We evaluated the anxiolytic and antidepressant effects of the aqueous extract of the bark of Tapinanthus dodoneifolius (TAE) (Danser) (25, 50, and 100 mg/kg), using open field, elevated plus maze, and forced swimming tests. Effect of TAE was compared to standard drugs diazepam (2 mg/kg) and imipramine (10 mg/kg). Additionally, the same doses of TAE were evaluated on rat's memory using Y-maze task. Results showed a significant (P < 0.05; 100 mg/kg) increase in the percentage of open arm entry and the time spent in the open arms in the elevated plus maze, suggesting an anxiolytic activity of the extract. In a dose-dependant manner, TAE at 25 mg/kg significantly (P < 0.05) decreased the number of lines crossed and the rearing behavior in the open field test, suggesting its possible sedative activity. In the forced swimming test, the immobility time of the animal was significantly reduced (P < 0.05) by TAE (100 mg/kg), compared to control, and this effect was quite comparable to that of imipramine. In the Y-maze paradigm, TAE at 50 mg/kg caused a significant increase in the spontaneous alternations but with a significant decrease in exploratory behavioral pattern. Taking these results together, TAE improved the spatial memory and showed anxiolytic, antidepressant, and sedative activities. The present results support the anxiolytic and antidepressant activities of TAE and, to our knowledge, for the first time, demonstrate its enhancing effect on memory.

Dexamethasone Regimens Alter Spatial Memory and Anxiety Levels in Mice

Acute and sub chronic effects of oral dexamethasone on anxiety and memory in mice were evaluated using the elevated plus maze, Y maze and radial arm maze. Adult male Swiss albino mice assigned to five groups were given vehicle (normal saline), a standard drug (Diazepam or Scopolamine) or one of three selected doses of dexamethasone (0.5, 1.0 and 1.5 mg/kg) daily for a period of 14 days. Behavioral tests were carried out on days 1 and 14 after administration. Results were analysed using a one-way ANOVA followed by a posthoc test (Student-Newman-Keul) and expressed as mean ± S.E.M. Elevated plus maze test showed a significant reduction in the time spent in the open arm and in the number of open arm entries compared to control. Results of radial arm and Y maze tasks showed an improvement in spatial memory following dexamethasone administration. Y maze locomotor activity was significantly increased, although radial arm maze exploration did not increase significantly. The study concluded that oral dexamethasone given either acutely or sub chronically has both anxiogenic and memory enhancing effects.

Involvement of Serotonergic System and Magnesium on Anxiolytic Effects of Pomegranate in Male Mice

The anxiolytic activities of Punica granatum L. fruit juice (PGFJ) in various validated animal models of anxiety and amnesia have been recently reported in mice. Similarly, anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in some studies. Buspirone is an anxiolytic psychoactive drug with known effects on 5-HT1A receptors that its action is not related to benzodiazepines. The purpose of the present study was to examine interactions between PGFJ, magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze in mice. The anxiolytic-like effect of PGFJ (5, 10 and 20 ml/kg, orally), buspirone (5 mg/kg, i.p), Mg (50 mg/kg, orally) and their interactions were evaluated after ten days’ treatment. PGFJ given at all doses induced an anxiolyticlike effect significantly increasing the percentage of the time spent in the open arms, and the percentage of the open arm entries, in a dose-dependent manner. Buspirone showed anxiolytic effect after ten days; however, its effect was roughly comparable to the effect of PGFJ 5 ml/kg. Buspirone in combination with PGFJ (5 ml/kg), did produce more effect compared to buspirone alone and nearly in the range of PGFJ 5 ml/kg response. Also, Mg induced an anxiolytic-like effect that was more than effects observed by buspirone 5 mg/kg. However, binary application of buspirone and Mg showed anxiolytic effects more than buspirone, alone. In another group, Mg in combination with PGFJ (5 ml/kg), produced more anxyolitic effects compared to either Mg or PEF alone. It can be concluded that Pomegranate anxyolitic-like effect is dependent on interactions with both GABAergic (related to Mg) and serotonergic (5-HT1A) systems.

Interactions of atenolol with alprazolam/escitalopram on anxiety, depression and oxidative stress

Anxiety and depression are highly comorbid disorders possibly sharing a common neurobiological mechanism. The dysfunction of serotoninergic, noradrenergic and dopaminergic neurotransmission, abnormal regulation in the hypothalamic–pituitary–adrenal axis (HPA), disturbance of cellular plasticity including reduced neurogenesis, or chronic inflammation connected with high oxidative damage play a crucial role in the development of anxiety and depression. The present study was aimed to investigate the effects of atenolol alone and in combination with alprazolam/escitalopram on anxiety, depression and oxidative stress. Wistar albino rats were subjected to 21day treatment of drugs then exposed to elevated-plus maze (EPM) and modified forced swim test (MFST), and oxidative stress markers were estimated in isolated brain tissue of all groups. The results indicated that atenolol in combination with alprazolam/escitalopram exhibited antidepressant effects by significantly decreasing the immobility and increasing the swimming behavior in the MFST and anti-anxiety effects by increasing the percentage preference and number of open arm entries as well as time spent in open arm in EPM. Pretreatment with atenolol alone and combination with alprazolam/escitalopram also ameliorated tissue glutathione (GSH) and decreased malondialdehyde (MDA) level significantly which explore antioxidant properties of drugs, and combination augments the therapeutic response of monotherapy in depression. In conclusion behavioral and biological findings indicate that the combination of atenolol with alprazolam/escitalopram has the potential of being highly efficacious in treating anxiety and depressive disorders as well as oxidative stress.

A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze

This work was performed to characterize the possible mechanisms involved in the anxiolytic-like activity of gallic acid (GA) in the rat elevated plus maze (EPM) test. Male Wistar rats were acutely treated with a single dose of GA (10–500mg/kg, i.p.) or diazepam and buspirone, 30min prior to behavioral assessment in the EPM, open-field and rotarod tests. Treatment with GA markedly produced an increase in the time spent and entries in the open arms of EPM at doses of 30 and 300mg/kg, respectively. These effects were comparable to those of the diazepam (1mg/kg, i.p.) and buspirone (1mg/kg, i.p.). Pretreatment with benzodiazepine antagonist flumazenil (3mg/kg, i.p.) partially blocked the anxiolytic-like effect of GA. However, an increase in the time spent and entries in the open arms of EPM observed with GA treatment were significantly inhibited by the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg, i.p.). In the open-field test, only GA at a dose of 500mg/kg decreased locomotor activity in rats. Moreover, GA (10–300mg/kg, i.p.) or diazepam and buspirone did not alter motor coordination in the rotarod test. These results indicate that GA is an effective anxiolytic agent at low doses, while at the highest dose it has sedative effect. Also this study suggests that the anxiolytic-like activity of GA is primarily mediated by the 5-HT1A but not benzodiazepine receptors.

Detection of anxiety and depression status of BALB/c asthmatic mice model

To detect the anxiety and depression status of BALB/c asthmatic model in mice. A total of 20 mice were randomly divided into asthma and control groups (n = 10 each). The animals were sensitized and challenged with ovalbumin for asthmatic model. Phosphate buffer solution was used in the control group. The mice were challenged with increasing concentrations of methacholine aerosol and the airway resistance was measuring non-invasively by enhanced pause (Penh). And elevated plus maze test system and forced swim were employed to evaluate their anxiety and depression status. Then bronchoalveolar lavage cytology was detected for evaluating the airway inflammation. In both groups, Penh value increased with the rising concentration of methacholine. The Penh values of asthmatic mice exciting with normal saline and methacholine concentration of 0, 5 g/L were 0.43 ± 0.04, 0.41 ± 0.05 and 0.44 ± 0.04 versus 0.42 ± 0.03, 0.39 ± 0.03,0.43 ± 0.04 in control group. The difference had no statistical significance (P = 0.290,0.652,0.723). At the concentration of methacholine 10, 15, 20 g/L, the Penh values of asthmatic mice were 0.57 ± 0.03,0.85 ± 0.04, 1.57 ± 0.08 and they were significantly higher than those of control group (0.45 ± 0.08,0.57 ± 0.06,0.82 ± 0.09) (P = 0.001,0.000,0.000). Asthmatic mice in the elevated plus maze on a behavioral test and found that asthmatic mice open arm entries sum closed arm entries (OE+CE), percent of open arm/total entries (OE%) and percent of open arm/total time (OT%) was (18.3 ± 3.6) times, (22.2 ± 3.1)%, (16.7 ± 4.2)%. They were significantly lower than those of control group ((24.0 ± 2.9) times,(28.0 ± 3.4)%, (21.8 ± 4.6)%) (P = 0.001,0.001,0.019). Asthmatic mice swimming time was significantly higher than that of control group (147 ± 12) vs (133 ± 10) s (P = 0.010). The total number of cells and eosinophil ratio in asthma group was (10.0 ± 4.0)×10(5)/ml and (68.18 ± 3.76)%. And they were significantly larger than those of control group ((1.7 ± 0.4)× 10(5)/ml, (0.12 ± 0.07)%) (both P = 0.000). Asthmatic mice with concurrent anxiety and depression may be a model for elucidating the molecular mechanisms of asthma with anxiety and depression.

Synthesis and psychobiological evaluation of modafinil analogs in mice

Background and the purpose of the studyModafinil, a novel wake-promoting agent with low potential for abuse and dependence, has a reliable structure to find some novel derivatives with better activity and lower potential for abuse and risk of dependency. This study was designed to evaluate psychobiological activity of some novel N-aryl modafinil derivatives.MethodsSeven novel N-aryl modafinil derivatives were synthesized through three reactions: a) preparation of benzhydrylsulfanyl acetic acid through reaction of benzhydrol with thioglycolic acid, b) formation of desired amide by adding the substituted aniline to activated acid with EDC (1-ethyl-3-(3-dimethyl amino propyl) carbodiimide). This reaction was catalyzed by HOBt (N- hydroxylbenzotriazole), and c) oxidation of sulfur to sulfoxide group with H2O2. Then, their psychobiological effect on the performance of male albino mice were compared to that of modafinil as following: wakefulness by determining the effects of derivatives on phenobarbital-induced loss of the righting reflex (LOPR); exploratory activity by measuring activity in the open field test (OFT); depression by measuring immobility time (IT) during forced swimming test (FST) and the anxiogenic and anxiolytic like effects by using elevated plus-maze test (EPM). All tests were videotaped and analyzed for the frequency and duration of the behaviors during the procedures.Conclusions2-(Benzhydrylsulfonyl)-N-(4-chlorophenyl)acetamide (4c) showed comparable result in LOPR test. However, all analogs were found to be stimulant except 2-(benzhydrylsulfinyl)-N-phenylacetamide (4a). Also 4c led the most exploratory activity in mice among derivatives. FST results showed that 4a had the longest IT while modafinil, 2-(benzhydrylsulfinyl)-N-(3-chlorophenyl) acetamide (4b) and 2-(benzhydrylsulfinyl)-N-(4-ethylphenyl) acetamide (4d) had the shortest IT. In EPM, all derivatives showed anxiogenic-like behavior since they decreased open arms time and open arms entries and simultaneously increased close arms time.

Androgen insensitive male rats display increased anxiety-like behavior on the elevated plus maze

Male rats carrying the testicular feminization mutation (Tfm-affected males) are insensitive to androgens, resulting in a female-typical peripheral phenotype despite possession of inguinal testes that are androgen secretory. Androgen-dependent neural and behavioral processes may likewise show atypical sexual differentiation. Interestingly, these mutant rats display elevated serum corticosterone, suggesting a chronic anxiety phenotype and dysregulated hypothalamic–pituitary–adrenal axis. In order to understand if elevated anxiety-like behavior is a possible mediating variable affecting the display of certain androgen-dependent behaviors, we compared the performance of Tfm-affected males to wild type males and females in the elevated plus maze (EPM). Two well-established indicators of anxiety-like behavior in the EPM were analyzed: total percentage of time spent on the open arms, and the percentage of open arm entries. We also analyzed the total number of open arm entries. Interestingly, Tfm-affected males spent less percentage of time on the open arms than both males and females, suggesting increased anxiety-like behavior. Percentage of open arm entries and the total number of arm entries was comparable between the groups, indicating that the observed decrease in the percentage of time spent on the open arms was not due to a global reduction in exploratory behavior. These data, in contrast to earlier reports, thus implicate androgen receptor-mediated functions in the expression of anxiety behaviors in male rats. Given that anxiety is widely reported as a precipitating factor in depression, studying the role of the androgen receptor in anxiety may give insights into the pathogenesis of major depressive disorder.

Fluoride exposure during development affects both cognition and emotion in mice

Previous studies have suggested that sodium fluoride (NaF) may have adverse effects on neurodevelopment. In the present study, we evaluated developmental neurotoxicity by assessing in cognitive function and emotional behavior in BalB/C mice treated with NaF. Mice were weaned at 4weeks, and water or different NaF concentrations (2, 5, or 10mg/L in drinking water) were provided for 4weeks. We found that exploration preference in the novel object recognition test was significantly altered in mice treated with 5 and 10mg/L NaF compared with the water-treated control animals. Furthermore, mice treated with 5 and 10mg/L NaF showed significantly longer escape latencies, less time in the target quadrant, and fewer platform-crossing numbers in the Morris water maze compared to those in the control group. In addition, mice treated with 10mg/L NaF spent a lower percentage of time in the open arms in the elevated-plus maze, while no significant changes were noted in the open and close arm entries or the total arm entries. We also found that the cumulative immobility time in the tail suspension test was longer in mice treated with 5 and 10mg/L NaF compared to the control group. Only 10mg/L NaF-treated mice showed longer immobility time compared with the control group. Collectively, our data indicate that developmental exposure to NaF induces cognitive deficits and anxiety-depression-like behaviors in mice.

Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice

Ethnopharmacological relevanceCarica papaya has been used in the Ethiopian traditional medicine to relieve stress and other disease conditions. Aim of the studyThe present study was undertaken to evaluate the anxiolytic and sedative effects of 80% ethanolic Carica papaya (Caricaceae) pulp extract in mice. Materials and methodsCarica papaya pulp extract was screened for anxiolytic effect by using elevated plus maze, staircase and open field tests, and ketamine-induced sleeping time test for sedation at doses of 50, 100, 200, 400mg/kg. Distilled water and Diazepam were employed as negative and positive control groups, respectively. ResultsCarica papaya pulp extract 100mg/kg significantly increased the percentage of open arm time and entry, and reduced the percentage of entry and time spent in closed arm in elevated plus maze test; reduced the number of rearing in the staircase test; and increased the time spent and entries in the central squares while the total number of entries into the open field were not significantly affected, suggesting anxiolytic activity without altering locomotor and sedative effects. A synergistic reduction in the number of rearing and an inverted U-shaped dose response curves were obtained with important parameters of anxiety ConclusionsThe results of this study established a support for the traditional usage of Carica papaya as anxiolytic medicinal plant.

Characterization of the anxiolytic and sedative profile of JM-20: a novel benzodiazepine–dihydropyridine hybrid molecule

Objectives: The aim of this study was to investigate the effects of oral administration of a novel benzodiazepine derivative, JM-20, on the neurological behavior of different rodent models, focusing on the GABAergic effect. We have also investigated the acute toxicity of oral administration of JM-20 in mice.Methods: Mice or rats received oral administration of JM-20 at 2, 4, 8, and 10 mg/kg to evaluate the sedative/hypnotic, anxiolytic, and anticonvulsant effects, as well as the influence on the stereotyped behavior induced by amphetamine. Diazepam (DZP) was used as a positive control. In addition, the mice received a single oral JM-20 dose of 2000 mg/kg to evaluate the acute toxicity.Results: In a dose-dependent manner, JM-20 (i) increased the number of crossings and decreased the number of rearings in the open-field test; (ii) decreased the aggressive behavior of socially-isolated mice; and (iii) increased the latency period for tonic seizure’s onset and the percentage of survival of animals with seizures. Moreover, JM-20 increased the sleeping time induced by barbiturates and the time spent and the number of entries in the open arms of the elevated plus-maze test. In the JM-20 toxicity test, no mortality was observed and only minor signs of toxicity associated with sedation were detected.Conclusions: These results indicate that JM-20 has an anxiolytic profile similar to DZP and its dihydropyridine moiety did not appear to interfere with the GABAergic activity associated with benzodiazepine. Furthermore, JM-20 did not show significant acute toxic effects in mice.

Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice

Studies showing anxiolytic-like properties of natural products have grown. This paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB) tests, and marble-burying tests (MBTs) were performed on mice. In the first protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam 1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were tested for GABAergic and serotonergic systems. The time spent in the open arms (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time spent in the light box (TSLB) and the number of entries to light box (NELB) were measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was not associated with psychomotor retardation in the open field test and in the Rota rod test, contrarily with what happened with DZP. In the second protocol, to suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY 100,635 10mg/kg ip (WAY–5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100 reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT, FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic agonist action, without psychomotor side effects.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: Modulation of hypothalamic–pituitary–adrenal axis activity and brain-derived neurotrophic factor level

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28days. Etazolate (0.5 and 1mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21days (8–28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic–pituitary–adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level.

The Essential Oil of &lt;i&gt;Myrtus communis&lt;/i&gt; L. Produces a Non-Sedating Anxiolytic Effect in Mice Models of Anxiety

The myrtle shrub (Myrtus communis L., Myrtaceae) is rich in essential oils used in Ethiopian traditional medicine for the treatment of a variety of ailments, including anxiety. Anxiety is a common disorder that attacks many people in society and often accompanied by physiological sensations such as tachycardia, chest pain, shortness of breath, and insensitivity. The present study was undertaken to evaluate the anxiolytic effect of the essential oil of M. communis using different models of anxiety. Swiss Albino mice of either sex were randomly divided into six groups. Tween 80 (5%, v/v) in distilled water was administered to Group I and served as control. Group II was given diazepam (0.5 mg/kg, orally) suspended in Tween 80 and served as standard. Group III-VI were given the essential oil at doses of 50, 100, 200 and 400 mg/kg, respectively. Animals were then subjected to different anxiety tests, including elevated plus maze (EPM), stair case and open field. Parameters, among others, percentage of time spent in each arm and arm entries, number of steps climbed and number of rears, and number of crossings were then measured. Data were presented as mean ± SEM and analyzed by ANOVA followed by Tuckey posthoc test. In EPM studies, the essential oil at both 100 mg/kg (p&lt;0.01) and 200 mg/kg (p&lt;0.05), as well as diazepam (p&lt;0.01) produced a significant increase in percentage of open arm time compared to controls. In the staircase setting, rearing was significantly decreased with 100 mg/kg (p&lt;0.01) and 200 mg/kg (p&lt;0.05) of the oil, and diazepam (p&lt;0.05) relative to controls. However, at doses of 50 mg/kg and 400 mg/kg no detectable changes were noted on the measured parameters in both EPM and stair case models. The total number of entries into open field was comparable in all groups. At a dose of 100 mg/kg, the essential oil of M. communis showed better anxiolytic activity than the standard drug. The possible mechanism by which the oil showed the activity could be through GABA-related mechanisms. The present work, therefore, holds up the traditional use of the plant for the treatment of anxiety.Keywords: Myrtus communis, essential oil, anxiety, elevated plus maze, stair case, open field

Increased nitric oxide-mediated neurotransmission in the medial prefrontal cortex is associated with the long lasting anxiogenic-like effect of predator exposure

Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by the experience of a severe traumatic event. In rats this disorder has been modeled by exposure to a predator threat. PTSD has been associated to structural and functional changes in the medial prefrontal cortex (mPFC). Direct injections into this brain region of glutamate antagonists or inhibitors of the nitric oxide synthase (NOS) enzyme cause anxiolytic-like effects in rodents. In the present work we investigated if the behavioral changes induced by predator exposure are associated with changes in the mPFC nitrergic system. Since the hippocampus, amygdala and dorsal periaqueductal grey have also been associated to anxiety disorders, including PTSD, we also verified if this procedure would modify the nitrergic system in these regions. Male Wistar rats were exposed to a dummy or live cat for ten minutes and tested in the elevated plus maze test (EPM) seven days later. Immediately after the test their brains were removed for neuronal NOS (nNOS) immunohistochemistry detection and measurements of nitrite/nitrate (NOx) levels. Exposure to the live cat increased freezing responses. One week later the animals that froze when confronted with the cat presented a decreased percentage of entries in the open arms of the EPM and an increased number of nNOS positive neurons in the mPFC and basolateral nucleus of amygdala, but not in the hippocampus, central and medial nuclei of amygdaloid complex or dorsal–lateral periaqueductal grey. Moreover, cat exposed animals showed increased NOx levels in the mPFC but not in the hippocampus one week later. The number of nNOS neurons and NOx levels in the mPFC showed a significant correlation with freezing time during cat exposure. Our results suggest that plastic modifications of the nitrergic system in the mPFC could be related to long lasting behavioral changes induced by severe traumatic events such as predator exposure.

S25 * UNITY IN DIVERSITY APSAAR, LASBRA &amp; ESBRA JOINT SYMPOSIUM

S25 * UNITY IN DIVERSITY APSAAR, LASBRA &amp; ESBRA JOINT SYMPOSIUM

Impact of Combined Prenatal Ethanol and Prenatal Stress Exposure on Anxiety and Hippocampal-Sensitive Learning in Adult Offspring

Prenatal ethanol (EtOH) and prenatal stress have both been independently shown to induce learning deficits and anxiety behavior in adult offspring. However, the interactive effects of these 2 developmental teratogens on behavioral outcomes have not been systematically evaluated. We combined an established moderate prenatal EtOH consumption paradigm where Long-Evans rat dams voluntarily consume either a 0 or 5% EtOH solution in 0.066% saccharin water (resulting in a mean peak maternal serum EtOH concentration of 84mg/dl) with a novel prenatal stress paradigm. Pregnant rats were exposed to 3% 2,3,5-trimethyl-3-thiazoline (TMT) for 20minutes a day on gestational days 13, 15, 17, and 19. Adult female offspring were evaluated for anxiety-like behavior using an elevated plus-maze and hippocampal-sensitive learning using a 2-trial trace conditioning (TTTC) task. TMT exposure produced a threefold increase in maternal serum corticosterone compared to nonexposed, unhandled controls. Neither prenatal exposure paradigm, either alone or in combination, altered maternal weight gain, EtOH consumption, maternal care of litters, litter size, pup birth weight, or pup weight gain up to weaning. Offspring exposed to prenatal stress displayed significant increases in anxiety-like behavior in the elevated plus maze in terms of open arm entries and time spent on the open arms, with no significant effect of prenatal EtOH exposure and no interaction of the 2 prenatal exposures. Performance in a TTTC task revealed a significant effect of prenatal EtOH exposure on freezing behavior on the testing day, with no significant effect of prenatal stress exposure and no interaction of the 2 prenatal exposures. While each prenatal exposure independently produced different behavioral outcomes, the results indicate that there is no significant interaction of prenatal EtOH and prenatal stress exposures on learning or anxiety at the exposure levels employed in this dual exposure paradigm. Subsequent studies will examine whether similar outcomes occur in male offspring and whether other measures of anxiety or learning are differentially impacted by these prenatal exposure paradigms.

Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats

This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02 percent capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology.

Involvement of the dorsal hippocampal dopamine D2 receptors in histamine-induced anxiogenic-like effects in mice

Anxiety-related behaviors increase histamine and dopamine release in the brain. On the other hand, central histamine counteracts reward and reinforcement processes mediated by the mesolimbic dopamine system. We investigated the effects of the histaminergic system and dopamine D2 receptors agents and their interactions on anxiety-related behaviors using the elevated plus-maze (EPM). The intra-hippocampal (Intra-CA1) microinjection of histamine (10μg/mouse) decreased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not the locomotor activity, indicating an anxiogenic-like response. Quinpirole (0.5 and 2μg/mouse) or sulpiride (0.3 and 1μg/mouse) when injected into the dorsal hippocampus also induced anxiety-like behavior, however, the drugs reversed the anxiogenic response induced by the effective dose of histamine (10μg/mouse). Taken together and under the present experimental design, our results indicate that activation of the dorsal hippocampal histaminergic receptors causes anxiety-like behaviors altered by dopamine D2 receptor agonist and antagonist. Histamine can decrease dopaminergic tone in the dorsal hippocampus through decreasing the endogenous dopamine release, whereas quinpirole does the same via the postsynaptic DA receptors’ activation. Sulpiride however renders the same effect through autoreceptors’ blockade and potentiated dopamine transmission. Thus, quinpirole and sulpiride seem to compensate the effects of the intra-CA1 injection of exogenous histamine, and tend to exert anxiolytic effects in the presence of histamine

Pharmacological effect of gelsemine on anxiety-like behavior in rat

The chemical compound gelsemine is the major active principle of the yellow jasmine (Gelsemium) that is generally claimed as possessing anxiolytic properties based on empirical and indirect knowledge. Surprisingly, gelsemine effect on anxiety has until now received only little attention. Here, we used the well-validated method for anxiety assessment, the elevated plus-maze combined with video-tracking, to measure gelsemine action on rat anxiety-like behavior. Rats were intraperitoneally injected (500μl/daily/7days) with gelsemine (10−6, 10−10 or 10−14M) or control solution. Diazepam (DZP) was used as positive standard anxiolytic and additional controls were naive rats similarly manipulated except being injected. Gelsemine or diazepam treatment did not affect the number of closed arm entries and rears illustrating the rat general activity. In contrast, gelsemine (10−6 to 10−10M) or DZP increased dose-dependently the number of entries and the percent of time spent in the open arms indicating that gelsemine is an anxiolytic. Consistently, we observed that gelsemine (10−6 to 10−10M) or DZP also decreased dose-dependently the percent of protected stretched attend postures, an ethological index of anxiety-like state. Altogether, our results constitute a solid set of fundamental data directly demonstrating anxiolytic properties of gelsemine. The report also opens new perspectives for the development of safe and effective gelsemine- or Gelsemium-based strategies against pathological anxiety.