Percentage Of Open Arm Entries Research Articles

Involvement of l-arginine-nitric oxide pathway in anxiolytic-like effects of zinc chloride in rats.

Zinc is crucial for normal development of the brain, and Zinc deficiency has been shown to associate with neurological disorders (e.g. anxiety) through interactions with several neurotransmitter systems such as nitric oxide (NO). In this regard, our study aimed to evaluate the possible involvement of l-arginine NO pathway on anxiolytic effects of zinc in adult male rats. Zinc chloride at doses of 2.5 and 10mg/kg (intraperitoneal or ip) or saline (1ml/kg, ip) were injected 30min before the anxiety test. Zinc administrated rats (10mg/kg) were pre-treated with intra-CA1 microinjection of l-arginine in sub-effective dose of 1μg/rat (dorsal hippocampus, vehicle: saline1μl/rat). In addition, zinc chloride and NG-nitro-l-arginine methyl ester (l-NAME) were intraperitoneally co-administrated in sub-effective doses of 2.5mg/kg and 80mg/kg, respectively. The percentage of open arm time (OAT%), percentage of open arm entry (OAE%), as measures of anxiety, and total number of arm entries, as measures of locomotor activity, were recorded. Treatment with zinc (10mg/kg) markedly produced an increase in OAT% and OAE% in the Elevated plus maze test (EPM). A decrease of OAT% and OAE% was shown in groups which received zinc (10mg/kg) and l-arginine (1μg/rat) concomitantly as compared to the control group. Moreover, an increase of OAE% was revealed in the group exposed to Zinc (2.5mg/kg) and l-NAME (80mg/kg) co-administration. Although, Two-way ANOVA showed no significant differences of anxiety indices in rats received drug+zinc chloride in compare to the zinc pretreated with saline group. Anxiolytic- like effect of zinc reversed by nitric oxide precursor l-arginine. Additionally, the synergistic effects of l-NAME and ZnCl2 were shown in the EPM. Thus our findings suggest that at least in part the anxiolytic effects of zinc can be mediated through the nitric oxide system.

CRF receptor type 1 (but not type 2) located within the amygdala plays a role in the modulation of anxiety in mice exposed to the elevated plus maze

The amygdala (Amy) is an important center that processes threatening stimuli. Among the neurotransmitters implicated in the control of emotional states, the corticotrophin releasing factor (CRF) is an important modulator, acting at CRF1 and CRF2 receptors. Few studies have investigated the role of CRF and its receptors in the Amy on anxiety in mice. Here, we investigated the effects of intra-Amy (aimed at the basolateral nucleus) injections of CRF (37.5 and 75pmol/0.1μl), urocortin 3 (UCn3, a selective CRF2 agonist; 4, 8, 16 or 24pmol/0.1μl), CP376395 (a selective CRF1 antagonist; 0.375, 0.75 or 1.5nmol/0.1μl), antisauvagine-30 (ASV-30, a selective CRF2 antagonist; 1 or 3nmol/0.1μl) on the behavior of mice exposed to the elevated plus maze (EPM). Both spatiotemporal (e.g., percentage of open-arm entries and percentage of open-arm time; %OE and %OT) and complementary [e.g., frequency of protected and unprotected stretched attend postures (pSAP and uSAP) and head dips (pHD and uHD); frequency and time spent on open arm end exploration (OAEE)] measures were recorded during a 5-min test in the EPM. While intra-Amy injections of CRF decreased %OE, %OT and OAEE, suggesting an anxiogenic-like action, UCn3 (all doses) did not change any behavior. In contrast, injections of CP376395 (0.75nmol) produced an anxiolytic-like effect, by increasing %OT and OAEE and decreasing pSAP and pHD. Neither spatiotemporal nor complementary measures were changed by intra-Amy ASV-30. These results suggest that CRF plays a marked anxiogenic role at CRF1 receptors in the amygdala of mice exposed to the EPM.

Small Nettle: Evaluation of Its Anxiolytic Effect in the Elevated Plus-Maze and Open Field

Background: Anxiety is a serious disorder affecting the world population. The most widely prescribed medications for anxiety disorders are the Benzodiazepines; however, they have prominent side effects. Thus, interest in alternative medicine that affects the ‘mind’ is growing. Among medicinal plants, Urtica urens has been recommended for relief of anxiety in Morocco folk medicine. Methods: The anxiolytic activity was evaluated with the adult mice by the elevated plus maze (EPM) and Open Field (OF) models of anxiety. The efficacy of the plant extract (100-600 mg/kg) was compared with the standard anxiolytic drug diazepam (1 mg/kg i.p.) Results: In the EPM, aqueous extract at 400mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries compared to control group. In an open field test aqueous extract of U. urens (400 mg/kg) increased the central area crossing, the time spent and number of rearing in the center of arena. Conclusions: These results provides support for anxiolytic activity of Urtica urens, in line with its medicinal traditional use, and may also suggest a better side-effect profile of Urtica urens relative to diazepam.

Sex-dependence of anxiety-like behavior in cannabinoid receptor 1 (Cnr1) knockout mice

Epidemiological data suggest women are at increased risk for developing anxiety and depression, although the mechanisms for this sex/gender difference remain incompletely understood. Pre-clinical studies have begun to investigate sex-dependent emotional learning and behavior in rodents, particularly as it relates to psychopathology; however, information about how gonadal hormones interact with the central nervous system is limited. We observe greater anxiety-like behavior in male mice with global knockout of the cannabinoid 1 receptor (Cnr1) compared to male, wild-type controls as measured by percent open arm entries on an elevated plus maze test. A similar increase in anxiety-like behavior, however, is not observed when comparing female Cnr1 knockouts to female wild-type subjects. Although, ovariectomy in female mice did not reverse this effect, both male and female adult mice with normative development were sensitive to Cnr1 antagonist-mediated increases in anxiety-like behavior. Together, these data support an interaction between sex, potentially mediated by gonadal hormones, and the endocannabinoid system at an early stage of development that is critical for establishing adult anxiety-like behavior.

Neurobehavioral changes and activation of neurodegenerative apoptosis on long-term consumption of aspartame in the rat brain

Though several studies on toxic effect of aspartame metabolite have been studied, there are scanty data on whether aspartame exposure administration could release formate, a methanol metabolite thereby inducing oxidative stress and neurodegeneration in brain discrete region. To mimic the human methanol metabolism, the methotrexate (MTX) treated folate deficient rats were used. Aspartame was administered orally to the MTX treated animals and was studied along with controls and MTX treated controls. Oral intubations of FDA approved 40 mg/kg b.wt aspartame were given daily for 90 days. The loco–motor activity and emotionality behavior in the aspartame treated animals showed a marked increase in the immobilization, fecal bolus with a marked decrease in ambulation, rearing, grooming. The anxiety behavior in the aspartame treated animals showed a marked decrease in percentage of open arm entry, percentage of time spent in open arm and number of head dips. It is appropriate to point out, formaldehyde and formate could have led to an increased formation of free radical in the aspartame treated animals resulting in altered neurobehavioral changes owing to neuronal oxidative damage. Aspartame induced ROS may be also linked to increased neuronal apoptosis. In this study the aspartame treated animals showed an up regulation in the apoptotic gene expression along with protein expression in the respective brain region indicating the enhancement of neuronal cell death. This study intends to corroborate that chronic aspartame consumption can alter the behavior and neurodegeneration in brain discrete regions.

Pharmacological and biochemical studies on the protective effects of melatonin during stress-induced behavioral and immunological changes in relation to oxidative stress in rats.

Stress is known to precipitate neuropsychiatric diseases, and depending upon its nature and intensity it can also influence the functioning of the immune system. Melatonin (N-acetyl-5-methoxy tryptamine) a pineal gland hormone and potent antioxidant is known to protect against many diseases. Effect of melatonin in stress-induced neuro-immunomodulation is not well elucidated. Therefore in the present study, the protective effects of melatonin were evaluated in restraint stress (RS)-induced behavioral and immunological changes in rats. RS for 1 h significantly reduces (i) percentage of open-arm entries and (ii) percentage of time spent on open-arm in elevated plus maze (EPM) test parameters (p < 0.01) and significant increase in MDA levels in brain homogenate when compared to non-RS control groups (p < 0.05). In immunological studies, both humoral and cell-mediated immune responses to antigen were significantly suppressed by RS for 1 h for 5 consecutive days, as evidenced by significant reduction in (i) anti-SRBC antibody titre, (ii) PFC counts, (iii) percentage change in paw volume, and (iv) Th1 (IFN-γ) and Th2 (IL-4) cytokine levels (p < 0.001 in all parameters). These RS-induced immunological changes were associated with significantly increased lipid peroxidation (MDA) levels in serum and significantly decreased activity of (i) SOD, (ii) CAT, and (iii) GSH levels in RS (X5)-exposed group (p < 0.02). Pretreatment with melatonin (10, 50, and 100 mg/kg) significantly reversed these RS-induced changes in EPM test parameters and humoral and cell-mediated immunological parameters, as well as oxidative stress markers in a dose-dependent manner by differential degrees (p < 0.001). Results are strongly suggestive of the involvement of free radicals during stress-induced neurobehavioral and immunological changes. These changes were significantly restored by melatonin pretreatment. We can conclude that melatonin may have a protective role during such stress-induced neuro-immunomodulation.

Behavioral and pharmacological investigation of anxiety and maternal responsiveness of postpartum female rats in a pup elevated plus maze

The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague–Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more than nulliparous rats. They also tended to spend more time in the open arms, indicating reduced anxiety. When tested with pups, postpartum rats retrieved pups into the closed arms, entered the open arms and closed arms more and had a higher moving speed than nulliparous rats, indicating increased maternal responsiveness. Both haloperidol (0.1 or 0.2mg/kg, sc) and fluoxetine (5 or 10mg/kg, ip) dose- and time-dependently decreased the percentage of time spent in the open arms and speed, but did not affect the percentage of open arm entries. Diazepam (1.0 or 2.0mg/kg, ip) did not affect pup retrieval, open arm time/entry in lactating rats. Thus, the percentage of open arm entries appears to be the most sensitive measure of anxiety in postpartum female rats, while speed could be used to index maternal responsiveness to pups, which are likely mediated by the dopamine D2 and serotonin transporter systems.

Risperidone Attenuates Modified Stress-Re-stress Paradigm-Induced Mitochondrial Dysfunction and Apoptosis in Rats Exhibiting Post-traumatic Stress Disorder-Like Symptoms.

Mitochondria play a significant role in the pathophysiology of post-traumatic stress disorder (PTSD). Risperidone and paroxetine were evaluated for their effect on mitochondrial dysfunction and mitochondria-dependent apoptosis in discrete brain regions in modified stress re-stress (SRS) animal model of PTSD. Male rats were subjected to stress protocol of 2 h restraint and 20 min forced swim followed by halothane anesthesia on day 2 (D-2). Thereafter, rats were exposed to re-stress (forced swim) on D-8 and at 6-day intervals on D-14, D-20, D-26, and D-32. The rats were treated with risperidone (0.01, 0.1, and 1.0 mg/kg p.o.) and paroxetine (10.0 mg/kg p.o.) from D-8 to D-32. Risperidone at median dose and paroxetine ameliorated modified SRS-induced depressive-like symptom (increase in immobility period) in forced swim, anxiety-like behavior (decrease in percentage of open arm entries and time spent) in elevated plus maze and cognitive deficits (loss in spatial recognition memory) in Y-maze tests on D-32. Risperidone, but not paroxetine, attenuated modified SRS-induced decreases in plasma corticosterone levels. Risperidone ameliorated increase in the activity of mitochondrial respiratory complex (I, II, IV, and V), decreases in the levels of mitochondrial membrane potential, cytochrome-C and caspase-9 in the hippocampus, hypothalamus, pre-frontal cortex, and amygdala. However, both drugs attenuated modified SRS-induced increase in the number of apoptotic cells and caspase-3 levels in all the brain regions indicating anti-apoptotic activity of these drugs. Hence, these results suggest that anti-apoptotic activity could be a common mechanism for anti-PTSD-like effect irrespective of the pathways of apoptosis in the modified SRS model.

Anxiolytic Effect of Borago officinalis (Boraginaceae) Extract in Male Rats

Background: Medicinal plants with natural antioxidants have been shown to be beneficial in a variety of complications such as anxiety. The elevated plus-maze (EPM) is one of the most widely used models to assess anxiety in small rodents. Objectives: This study was designed to characterize the anxiolytic-like activity of Borago officinalis (Linnaeus, family Boraginaceae) or Borage flowers extract, using an EPM test. Materials and Methods: Male Wistar rats weighing 220-250 grams were used in the present study. Thirty minutes after an intraperitoneal (IP) injection of the Borage extract (50, 100, 200 mg/kg) or saline, each animal was placed in the EPM. Animal behaviors in the experimental sessions were recorded by a video camera located above the maze, interfaced with a monitor and a computer in an adjacent room. The time spent in the open arms, the percentage of entries into the open arms of the EPM and the numbers of entries into the closed arms were recorded for five minutes. Results: Statistical analysis indicated that acute IP injection of Borage extract before an EPM trial significantly increased the time spent in open arms and percentage of open arms entries. Whereas, the extract had no effect on the number of closed arm entries. Conclusions: Our results demonstrated that injection of Borage extract might have an anxiolytic profile in rats. However, the exact mechanism (s) related to the active compound (s) in Borage extract should be elucidated in future studies.

Blockade of mGluR5 in the nucleus accumbens shell but not core attenuates heroin seeking behavior in rats.

Glutamatergic neurotransmission in the nucleus accumbens (NAc) is crucial for the relapse to heroin seeking. The aim of this study was to determine whether mGluR5 in the NAc core or shell involved in heroin seeking behavior in rats. Male SD rats were self-administered heroin under a fixed-ratio 1 (FR1) reinforcement schedule for 14 d, and subsequently withdrawn for 2 weeks. The selective mGluR5 antagonist 2-methyl-6-phenylethynyl-pyridine (MPEP, 5, 15 and 50 nmol per side) was then microinjected into the NAc core or shell 10 min before a heroin-seeking test induced by context, cues or heroin priming. Microinjection of MPEP into the NAc shell dose-dependently decreased the heroin seeking induced by context, cues or heroin priming. In contrast, microinjection of MPEP into the NAc core did not alter the heroin seeking induced by cues or heroin priming. In addition, microinjection with MPEP (15 nmol per side) in the NAc shell reversed both the percentage of open arms entries (OE%) and the percentage of time spent in open arms (OT%) after heroin withdrawal. Microinjection of MPEP (50 nmol per side) in the striatum as a control location did not affect the heroin seeking behavior. Microinjection of MPEP in the 3 locations did not change the locomotion activities. Blockade of mGluR5 in NAc shell in rats specifically suppresses the relapse to heroin-seeking and anxiety-like behavior, suggesting that mGluR5 antagonists may be a potential candidate for the therapy of heroin addiction.

EVALUATION OF NEUROPHARMACOLOGICAL ACTIVITY OF PUNICA GRANATUM L. PEELS IN EXPERIMENTAL RATS

Extracts of peels of Punica granatum L. were screened for neuropharmacological activities viz. antianxiety, analgesic and learning and memory activities, using Elevated Plus Maze (EPM), Hot Plate Analgesiometer and Morris Water Maze, respectively. Aqueous extract of the peels (200mg/kg) and ethanolic extracts (200mg/kg and 400mg/kg) were administered by oral route for seven days. The control used was 1% Tween 80. Diazepam (4 mg/kg) and pentazocine (5 mg/kg) were used as standard drugs. Phytochemical analysis of the extracts was conducted. The rats receiving the ethanolic extract at a dose of 400mg/kg showed a significant increase in percentage open arm entries and percentage time spent in open arms in the EPM test thus indicating anti-anxiety activity. All the three extracts showed significant increase in reaction time on the hot plate analgesiometer and significant decrease in latency in the Morris Water Maze test, thus demonstrating analgesic activity and memory enhancement.

High maternal choline consumption during pregnancy and nursing alleviates deficits in social interaction and improves anxiety-like behaviors in the BTBR T + Itpr3tf/J mouse model of autism

Autism is a neurodevelopmental disorder with multiple genetic and environmental risk factors. Choline is a fundamental nutrient for brain development and high choline intake during prenatal and/or early postnatal periods is neuroprotective. We examined the effects of perinatal choline supplementation on social behavior, anxiety, and repetitive behaviors in the BTBR T+Itpr3tf/J (BTBR) mouse model of autism. The BTBR or the more “sociable” C57BL/6J (B6) strain females were fed a control or choline-supplemented diet from mating, throughout pregnancy and lactation. After weaning to a control diet, all offspring were evaluated at one or two ages [postnatal days 33–36 and 89–91] using open field (OF), elevated plus maze (EPM), marble burying (MB), and three-chamber social interaction tests. As expected, control-diet BTBR mice displayed higher OF locomotor activity, impaired social preference, and increased digging behavior during the MB test compared to control-diet B6 mice. Choline supplementation significantly decreased digging behavior, elevated the percentage of open arm entries and time spent in open arms in the EPM by BTBR mice, but had no effect on locomotion. Choline supplementation did not alter social interaction in B6 mice but remarkably improved impairments in social interaction in BTBR mice at both ages, indicating that the benefits of supplementation persist long after dietary choline returns to control levels. In conclusion, our results suggest that high choline intake during early development can prevent or dramatically reduce deficits in social behavior and anxiety in an autistic mouse model, revealing a novel strategy for the treatment/prevention of autism spectrum disorders.

Anxiolytic Effects of Acute Injection of Hydro-Alcoholic Extract of Lettuce in the Elevated Plus-Maze Task in Rats

Background: Anxiety is a physiological state characterized by cognitive, somatic, emotional, and behavioral components. There is some evidence in traditional medicine for the effectiveness of lettuce ( Lactuca sativa) in the treatment of anxiety in humans. Objectives: The present study investigated the effects of a hydro-alcoholic extract of lettuce on rat behavior in the elevated plus-maze (EPM) and the results compared with the effects of diazepam. Materials and Methods: Adult male Wistar rats weighing 200 - 240 g were used in the present study. Seven different groups of rats received an intraperitoneal (IP) injection of lettuce extract (50, 100, 200 mg/kg), diazepam (0.3, 0.6, or 1.2 mg/kg), or vehicle (control group), 30 minutes before entering the EPM test. The total distance covered by the animals, the percentage of entries into the open arms of the EPM, the time spent in the open arms, and the number of entries into the closed arms were recorded for a 5 minutes duration. Results: An IP injection of both diazepam and lettuce extract before an EPM trial significantly increased the percentage of open arm entries and the time spent in the open arms. Diazepam decreased the total distance covered by the animals and the number of closed arm entries, whereas lettuce extract had no effect on these parameters. Locomotor activity was not significantly changed by the lettuce extract. Conclusions: Acute administration of lettuce extract has an anxiolytic profile in rats similar to that of anxiolytic diazepam at low dose. Future investigations are essential for better understanding of the anxiolytic properties and neurobiological mechanisms of lettuce extract.

Anxiolytic effects of prelimbic 5-HT1A receptor activation in the hemiparkinsonian rat

This study sought to assess whether unilateral lesions of the medial forebrain bundle (MFB) using 6-hydroxydopamine in rats are able to induce anxiety-like behaviors, the role of serotonin-1A (5-HT1A) receptors of the prelimbic (PrL) sub-region of ventral medial prefrontal cortex in the regulation of these behaviors, the density of 5-HT neurons in the dorsal raphe nucleus (DRN) and co-localization of 5-HT1A receptor and neuronal glutamate transporter EAAC1-immunoreactive (EAAC1-ir) cells in the PrL. Unilaterally lesioning the MFB induced anxiety-like behaviors as measured by the open-field and elevated plus maze tests when compared to sham-operated rats. Intra-PrL injection of 5-HT1A receptor agonist 8-OH-DPAT (50, 100, and 500ng/rat) decreased the percentage of time spent in the center of the open-field and percentages of open arm entries and open arm time in sham-operated rats, indicating the induction of anxiogenic responses, and administration of 5-HT1A receptor antagonist WAY-100635 (60, 120, and 240ng/rat) showed anxiolytic effects. However, 8-OH-DPAT, at the same doses, increased the percentage of time spent in the center of the open-field and percentages of open arm entries and open arm time in the lesioned rats, indicating the induction of anxiolytic effects, and WAY-100635 produced anxiogenic responses. Unilateral MFB lesion decreased the density of 5-HT neurons in the DRN, and percentage of EAAC1-ir cells expressing 5-HT1A receptors in the PrL. These results suggest that unilateral lesions of the MFB in rats may induce anxiety-like behaviors, and activation of 5-HT1A receptors in the PrL has anxiolytic effects in the rat model of Parkinson's disease.

Effect of a selective cyclooxygenase type 2 inhibitor celecoxib on depression associated with obesity in mice: an approach using behavioral tests.

The biological mechanisms that link the development of depression to metabolic disorders such as obesity and diabetes remain ambiguous. In the present study the potential of a selective cyclooxygenase inhibitor celecoxib (15mg/kgp.o.) was investigated in depression associated with obesity in mice. Behavioral tests used to assess depressive-like behavior were sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM). The basal locomotor score in obese mice was not altered. Furthermore, estimation of biochemical parameters was performed for plasma glucose, total cholesterol, triglycerides and total proteins. Escitalopram (10mg/kgp.o.) served as reference standard drug. In the results, chronic treatment with celecoxib for 28days significantly attenuated the behavioral alterations as indicated by increased the sucrose consumption, reduced the immobility time in FST and TST, increased the percent open arm time and entries in EPM in obese mice. In the biochemical parameters celecoxib significantly reversed the increased plasma glucose, total cholesterol, triglycerides and total proteins in obese mice. In conclusion, celecoxib exhibited potential antidepressant-like effect in depression associated with obesity, which to some extent is mediated by reversing the altered plasma glucose in obese mice.

Insulin reverses anxiety-like behavior evoked by streptozotocin-induced diabetes in mice.

Clinical and preclinical data suggest that diabetes is often associated with anxiety. Insulin, a peptide hormone has been reported to have key functions in the brain and in alleviating several psychological impairments, occur as a consequence of diabetes. However, its effects in diabetes-induced anxiety are scanty. The present study examined whether; insulin can reverse the anxiety-like behavior in streptozotocin (STZ)-induced diabetes in mice. After 8-weeks of diabetes induced by STZ (200 mg/kg, intraperitoneally (i.p.)), mice were given insulin (1-2 IU/kg/day, i.p.)/ diazepam (1 mg/kg/day, i.p.)/ vehicle for 14 days and evaluated for behavioral effects in three validated models of anxiety viz. elevated plus maze (EPM), light-dark (L/D) and hole board (HB) tests. STZ-induced diabetic mice elicited significant behavioral effects which include, decreased percentage open arm entries and time in EPM, reduced latency and time spent in light chamber in L/D, decreased number of head dips, squares crossed and rearings in HB tests respectively. Insulin treatment attenuated the behavioral effects evoked by STZ-induced diabetes in mice as indicated by increased open arms activity in EPM, decreased aversion in light chamber during L/D test and increased exploratory behavior in HB test. In conclusion, this study revealed that insulin can reverse anxiety-like behavior in STZ-induced diabetes in mice.

Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats

It is yet unclear if ethanol-induced motor stimulation in the open field (OF) merely reflects psychomotor stimulating effects of the drug or if this stimulation is driven or modulated by ethanol's antianxiety properties. In the present study, adolescent rats were administered with different ethanol doses or remained untreated. They were sequentially assessed in the OF, elevated plus maze (EPM), and light-dark box (LDB) and then assessed for ethanol intake. The aims were to assess the relationship between measures of ethanol-induced activity and anxiolysis, analyze ethanol intake as a function of prior ethanol exposure, and associate behavioral responsiveness in these apparatus with ethanol intake during adolescence. The results suggested that the enhanced exploration of the OF observed after 2.5 and 3.25 g/kg ethanol reflected a motor-stimulating effect that appeared to be relatively independent of anxiolysis. The 1.25 g/kg dose induced motor stimulation in the OF and anti-anxiety effects in the EPM, but these effects were relatively independent. The 0.5 g/kg ethanol dose exerted significant anxiolytic effects in the EPM in the absence of stimulating effects in the OF. A multivariate regression analysis indicated that adolescents with a higher frequency of rearing behavior in the OF, higher percentage of open arm entries in the EPM, and lower propensity to enter the central area of the OF exhibited greater ethanol intake. These results indicate that the OF is a valid procedure for the measurement of ethanol-induced stimulation, and provide information toward characterizing subpopulations of adolescents at risk for initiating alcohol drinking.

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.

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.

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.