Light-dark Exploration Test Research Articles

Phytochemical and pharmacological evaluation of bacopa monniera for anti – anxiety activity

Anxiety, a common emotional response to stress, involves numerous brain regions and neurotransmitters, including the amygdala, prefrontal cortex, and hippocampus, and is partially by genetic, environmental, and biological factors. This study evaluates Bacopa monnieri, a herb known in Ayurvedic medicine for its cognitive-enhancing and adaptogenic properties, as a potential anti-anxiety agent. The plant's ethanolic extract revealed a variety of phytochemicals, including alkaloids, flavonoids, and saponins. Acute toxicity studies indicated a high safety margin with an LD50 exceeding 2000 mg/kg body weight. The anti-anxiety effects were assessed using three established models. In the Elevated Plus-Maze Test, Bacopa monnieri significantly reduced anxiety levels in mice, comparable to the standard anxiolytic benzodiazepine. The Hole-Board Test showed increased head-dipping and rearing behaviors, while reducing immobility, suggesting anxiolytic activity. The Light-Dark Exploration Test demonstrated the herb's ability to decrease anxiety-related behaviors, including a reduction in rearing in dark compartments and increased exploration of light areas. These findings provide scientific validation for Bacopa monnieri's traditional use in treating anxiety and support its potential as an effective and safe anti-anxiety agent in managing central nervous system disorders.

Higher exploratory and vigilant behaviors related to higher central dopaminergic activities of Formosan wood mice (Apodemus semotus) in light-dark exploration tests

Formosan wood mice (Apodemus semotus) are endemic rodents in Taiwan. Recently Formosan wood mice exhibit similar locomotor behaviors in the laboratory environment as in the field environment has shown. Contemporaneously, Formosan wood mice have higher moving distances of and central dopaminergic (DAergic) activities than C57BL/6 mice in behavioral test. This study tried to compare the behavioral responses between male Formosan wood mice and male C57BL/6 mice in the light-dark exploration tests. We also measured the levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC), the primary metabolite of DA, to assess the dopaminergic activity of the medial prefrontal cortex, striatum, and nucleus accumbens. Our data show that Formosan wood mice revealed higher exploration and central DAergic activities than did C57BL/6 mice in the light-dark exploration tests, and diazepam (an anxiolytics) treatment reduced the exploratory activity and central dopaminergic activities in Formosan wood mice, but not in C57BL/6 mice. After repeated exposure to light-dark exploration tests, the latency to dark zone was increased, and the duration in light zone as well as the central DAergic activity were decreased in C57BL/6 mice. This study provides comparative findings; Formosan wood mice showed the higher exploratory activities than C57BL/6 mice did, and their central DAergic activities were related to the behavioral responses in these two mice. This could potentially shed light on the reasons behind the prevalence of higher exploration and central dopaminergic activities. Using Formosan wood mice as a model to study human diseases related to hyperactivity adds significant value to the potential research.

Anxiolytic and antidepressant effects of agarwood inhalation and its mechanism

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.

Agarwood essential oil inhalation exerts antianxiety and antidepressant effects via the regulation of Glu/GABA system homeostasis.

Depression and anxiety are common diseases that endanger the physical and mental health of individuals. Agarwood incense inhalation has been used as a traditional Chinese medicine for relaxation and to improve sleep for centuries. In a previous study by the authors it was demonstrated that agarwood essential oil (AEO) injection exerted anxiolytic and antidepressant effects. Therefore the present study further investigated the anxiolytic and antidepressant effects of AEO inhalation on anxiolytic mice induced by M-chlorophenylpiperazine and depressive mice induced by chronic unpredictable mild stress. The results demonstrated that AEO exerted a significant anxiolytic effect, whereby autonomous movements were inhibited during the light dark exploration test and open field test. Furthermore, the tail suspension test and the forced swimming test demonstrated that AEO also exerted an antidepressant effect, whereby the immobility times were decreased. Moreover, AEO was determined to increase the levels of 5-hydroxytryptamine, γ-aminobutyric acid (GABA) A receptor (GABAA) and glutamate (Glu) in anxiolytic mice and inhibit the levels of GABAA and Glu in depressive mice. Further investigations into how AEO affected the Glu/GABA system demonstrated that AEO markedly increased the protein expression levels of GABA transaminase (GABAT), glutamate metabotropic receptor 5 (GRM5), glutamate ionotropic receptor AMPA type subunit 1 (GluR1) and vesicular glutamate transporter 1 (VGluT1). Furthermore, AEO reduced the expression levels of GABAT, glutamate ionotropic receptor NMDA type subunit 2B and GRM5, and enhanced the expression levels of GluR1 and VGluT1. These results demonstrated that AEO potentially possesses antianxiety and antidepressant properties. The present study determined that the mechanism was related to the regulation of Glu/GABA neurotransmitter system homeostasis.

The Impact of Obesity and Consumption of a High Fat Diet on Anxiety-Like Behavior in Mice

Abstract Objectives This study sought to measure the behavioral effects of consumption of a high-fat diet (HFD) on anxiety-like and depression-like behaviors in mice. It is hypothesized that animals consuming a HFD would exhibit more anxiety-like and depressive-like behaviors than their counterparts consuming a control diet. Methods Thirty C57BL6 mice were separated into two groups (n = 15/each) and placed on either a HFD (60% from fat) or control diet (CD) (10% from fat) for four months prior to behavioral testing. Anxiogenic behavior was assessed by three behavioral measures: (1) marble burying, during which the number of marbles buried in bedding was recorded as an index of compulsive behavior, (2) light-dark exploration, in which time spent in the brightly-lit chamber was considered an index of anti-anxiety-like behavior and (3) the open field test, in which time spent in the brightly-lit center of the field was recorded as an index of anti-anxiety-like behavior. Depression-like behavior was assessed using the forced swim test, during which immobility was measured as an index of behavioral despair. Furthermore, the stress hormone corticosterone and the cytokine interleukin-6 (IL-6) were measured (in urine and cortex, respectively). Results The mice fed HFD demonstrated more anxiety-like behaviors than the CD mice. The HFD-fed mice spent significantly less time in the brightly-lit chamber in light-dark exploration test and significantly less time in the center of the open field compared to the CD mice. The number of marbles buried was significantly correlated with weight and locomotor activity and thus, could not be attributed to anxiety. Analysis of the forced swim test did not reveal any significant differences in the time spent immobile or latency to immobility between the two diet groups. Urinary analysis of corticosterone levels showed greater levels of the stress hormone in the HFD-fed mice. There was also a significant increase in IL-6 in the cortex of the mice fed HFD. Conclusions These data demonstrated that HFDs increased anxiety-like, but not depressive-like behaviors in mice. This anxiogenic behavior was associated with increased stress hormone and inflammation, however, further research is needed to determine if this association is also observed in humans. Funding Sources Summer Undergraduate Research Program at Simmons (SURPASs).

Impact of Exposure to Environmental Enrichment on the Anxiety-Like Behavior of Ovariectomized Mice

Objective: The aim of this study was to explore the influence of short-term (2-week) exposure to social (SE) and/or physical enrichment (PE) on the anxiety-like behavior of ovariectomized (OVX) NIH Swiss mice. Method : One week after surgery, each OVX mouse was housed under one of 4 social conditions: (1) isolated, (2) accompanied by an intact female, (3) accompanied by an intact male, or (4) in a community of 10 OVX individuals. The animals in each of these environments were divided into 2 subgroups, consisting of the presence and absence of PE. Following a 2-week exposure to the respective conditions, each OVX mouse was subjected to either the light/dark exploration test (LDT) or the elevated plus maze (EPM) to examine anxiety-like behavior. Results: The LDT and EPM showed very similar patterns. Compared to an impoverished environment, PE elicited a significant anxiolytic effect for OVX mice housed alone or in companion of an intact female (F [1, 54] = 16.11, P = 0.001). By contrast, mice living in community but without PE displayed anxiogenic-like behavior, perhaps due to crowding, compared to the animals living in isolation (F [1, 36] = 5.64, P = 0.023). Conclusion: This study emphasized the importance of taking housing conditions into account during the screening of new anxiolytic agents and the critical role of OVX in the regulation of anxiety.

Increased anxiety-like behavior following circuit-specific catecholamine denervation in mice

Parkinson's disease (PD) presents with a constellation of non-motor symptoms, notably increased anxiety, which are currently poorly treated and underrepresented in animal models of the disease. Human post-mortem studies report loss of catecholaminergic neurons in the pre-symptomatic phases of PD when anxiety symptoms emerge, and a large literature from rodent and human studies indicate that catecholamines are important mediators of anxiety via their modulatory effects on limbic regions such as the amygdala. On the basis of these observations, we hypothesized that anxiety in PD could result from an early loss of catecholaminergic inputs to the amygdala and/or other limbic structures. To interrogate this hypothesis, we bilaterally injected the neurotoxin 6-OHDA in the mouse basolateral amygdala (BL). This produced a restricted pattern of catecholaminergic (tyrosine-hydroxylase-labeled) denervation in the BL, intercalated cell masses and ventral hippocampus, but not the central amygdala or prefrontal cortex. We found that this circuit-specific lesion did not compromise performance on multiple measures of motor function (home cage, accelerating rotarod, beam balance, pole climbing), but did increase anxiety-like behavior in the elevated plus-maze and light-dark exploration tests. Fear behavior in the pavlovian cued conditioning and passive avoidance assays was, by contrast, unaffected; possibly due to preservation of catecholamine innervation of the central amygdala from the periaqueductal gray. These data provide some of the first evidence implicating loss of catecholaminergic neurotransmission in midbrain-amygdala circuits to increased anxiety-like behavior. Our findings offer an initial step towards identifying the neural substrates for pre-motor anxiety symptoms in PD.

Agarwood Essential Oil Ameliorates Restrain Stress-Induced Anxiety and Depression by Inhibiting HPA Axis Hyperactivity.

In our previous investigation, we found that agarwood essential oil (AEO) has a sedative-hypnotic effect. Sedative-hypnotic drugs usually have an anxiolytic effect, where concomitant anxiety and depression are a common comorbidity. Therefore, this study further investigated the anxiolytic and antidepressant effects of AEO using a series of animal behavior tests on a restraint stress-induced mice model. The elevated plus maze (EPM) test, the light dark exploration (LDE) test, and the open field (OF) test demonstrated that AEO has a significant anxiolytic effect. Simultaneously, the tail suspension (TS) test and the forced swimming (FS) test illuminated that AEO has an antidepressant effect with the immobility time decreased. Stress can cause cytokine and nitric oxide (NO) elevation, and further lead to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. AEO was shown to dose-dependently inhibit the levels of cytokines, including interleukin 1α (IL-1α), IL-1β, and IL-6 in serum, significantly decrease the mRNA level of neural nitric oxide synthase (nNOS) in the cerebral cortex and hippocampus, and inhibit the nNOS protein level in the hippocampus. Concomitant measurements of the HPA axis upstream regulator corticotropin releasing factor (CRF) and its receptor CRFR found that AEO significantly decreases the gene expression of CRF, and significantly inhibits the gene transcription and protein expression of CRFR in the cerebral cortex and hippocampus. Additionally, AEO dose-dependently reduces the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) downstream of the HPA axis, as measured by ELISA kits. These results together demonstrate that AEO exerts anxiolytic and antidepressant effects which are related to the inhibition of CRF and hyperactivity of the HPA axis.

GABA neurons of the ventral periaqueductal gray area modulate behaviors associated with anxiety and conditioned fear.

Emotional behavioral responses related to anxiety and fear comprise the negative valence systems domainas defined by the Research Domain Criteria (RDoC) approach to categorizing related emotional behavioral constructs that are compromised in mental health disorders. Here, we evaluate the role of GABA neurons of the ventral periaqueductal gray (vPAG) in emotional behavioral responses related to anxiety and fear using a chemogenetic approach in Vgat-ires-Cre mice. Functional inhibition of vPAG GABA neurons using selective expression of inhibitory Gi-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gi-DREADDs) enhanced anxiety-like behavior in the light-dark exploration and open-field tests. Functional inhibition of vPAG GABA neurons during the acquisition of conditioned fear impaired later performance of conditioned fear responses to the fear-associated context. No effects on spontaneous freezing behavior, fear generalization, or conditioned fear responses to the fear-associated cue were observed. Together, these data suggest that activity of vPAG GABA neurons underlies emotional behavioral responses related to anxiety and conditioned fear. As such, vPAG GABA neurons are a common neurophysiological correlate of the negative valence system and dysregulation of this population may contribute to the etiology of mental health disorders in which the negative valence systems domain is compromised.

Screening of Antistress and Anxiolytic Activities of Piper longum Fruits Extract

The aim of the study was to investigate adaptogenic and anxiolytic activities of methanol extract of Piper longum fruits at different dose levels (100, 250 and 500 mg/kg) using different experimental animal models. In the present research work antistress activity was assessed by swimming endurance and immobilization stress models, and anxiolytic activity were assessed by elevated plus maze behavior of mice, light dark exploration test in mice and open field apparatus test in rats. In swimming endurance test, the mean time of swimming performance and swimming stress induced biochemical parameters such as serum cortisol, the weights of adrenal glands, ascorbic acid and cortisol levels were recorded in the adrenal gland. There was dose dependent significant increase in swimming performance time observed in mice pretreated with graded doses of the test extracts. Animals pretreated with test extracts at different dose levels showed significant and dose dependent fall in all the biochemical parameters, as compared to the stress control animals. Treatment with standard and test extracts significantly reversed the stress induced altered hematological parameters, biochemical parameters, organs weight, GSH and LPO levels and neurotransmitters such as dopamine, nor adrenaline and serotonin levels in rat brain In immobilization stress. The test extracts demonstrated the significant increase in time spent and number of entries into open arm in elevated plus maze apparatus test and also increase in time spent and number of entries into lit box was observed in light box exploration test and reduction in time spent and number crossing into the dark compartment observed in animals pretreated with test extract. Pretreatment with test extracts demonstrated dose dependent significant increase in ambulation, rearing and self-grooming and significant decrease in fecal dropping in case of open field test.

Emotional disorders induced by Hemopressin and RVD-hemopressin(α) administration in rats.

The endocannabinoid (eCB) system plays an important role in regulating emotional disorders, and is involved, directly or indirectly, in psychiatric diseases, such as anxiety and depression. Hemopressin, a hemoglobin α chain-derived peptide, and RVD-hemopressin(α), a N-terminally extended form of hemopressin, act as antagonist/inverse agonist and negative allosteric modulator of the cannabinoid 1 (CB1) receptor, respectively. Considering the possible involvement of these peptides on emotional behaviour, the aim of our study was to investigate the behavioural effects of a single intraperitoneal (ip) injection of hemopressin (0.05mg/kg) and RVD-hemopressin(α) (0.05mg/kg), using a series of validated behavioural tests (locomotor activity/open field test, light-dark exploration test, forced swim test) in rats. Prefrontal cortex levels of norepinephrine (NE), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) and the gene expression of monoamine oxidase (MAO-B) and catechol-O-methyltransferase (COMT) were measured by high performance liquid chromatography (HPLC) analysis and real-time reverse transcription polymerase chain reaction (RT-PCR), respectively. Hemopressin administration induced anxiogenic and depressive behaviour, decreased monoamine steady state levels in prefrontal cortex, and increased the gene expression of the enzymes involved in their catabolism. By contrast, RVD- hemopressin(α) induced anxiolytic and antidepressive effects, increased monoamines and decreased the enzymes in prefrontal cortex. In conclusion, in the present study we demonstrated behavioral effects induced by peripheral hemopressin and RVD-hemopressin(α) injections, that could involve modulatory effects on monoaminergic signaling, in the prefrontal cortex.

English

Research in the area of herbal psychopharmacology has increased considerably over the past few decades in search of panacea for neuroprotection. Seaweeds are one of the herbal sources consumed in many Asian countries as medicine due to their remarkable bioprospecting properties and evident health benefits. Keeping in view the bioactive potential of seaweeds, the present study was designed to evaluate the psychotherapeutic potential of Sargassum swartzii and Stoechospermum marginatum, in association with the role of brain norepinephrine (NE) using a rat model. Adult male albino Wistar rats were divided into three groups (n=6) as control rats (CR), S. swartzii extract treated (SSET) and S. marginatum extract treated (SMET). Seaweeds were extracted using methanol and administered orally to rats for four weeks at a dose of 60 mg/kg. Behavioral changes for stimulant activities were assessed by activity cage and open field tests, while anxiety was observed in light-dark exploration test. Followed by scoring behavioral activities, rats were decapitated and brain samples taken out from the cranial cavity were immediately stored at -70°C until estimation of brain NE levels by high performance liquid chromatography-electrochemical detection (HPLC-ECD). Results exhibited an increase in ambulatory and anxiolytic activities by SSET and SMET rats with subsequent increase in brain NE as compared to CR. The increase in NE in SSET and SMET rats could be attributed to the lipolytic activity of seaweeds. However, the exact mechanism underlying the increase in NE needs further investigations. In conclusion, seaweed extracts showed significant psychostimulant and anxiolytic activity by ameliorating brain NE levels and could be studied further for isolation of active ingredients responsible for eliciting such a response. Key words: Brown seaweeds, norepinephrine, psychostimulant activity, anxiety.

Exposure to short photoperiod regime reduces ventral subicular lesion-induced anxiety-like behavior in Wistar rats

Neurodegeneration of hippocampal structures is implicated in Alzheimer's disease (AD). Patients with AD exhibit ‘sundown syndrome’ featuring mood swings and anxiety. Although there are studies demonstrating circadian rhythm disruption associated with sundown phenomenon, the mechanisms underlying the emotional disturbances remain elusive. In the present study, we examined the relationship between subiculum (a key hippocampal output structure) and anxiety. Our study demonstrates that bilateral ventral subicular lesion (VSL) leads to anxiogenic behavior. In the elevated plus maze test, VSL rats made less number of entries into the open arms and spent significantly more time in the closed arms. Similarly, in the light–dark exploration test, VSL rats spent significantly more time in the dark chamber and made fewer entries into the light chamber. VSL also produced significant neurodegeneration in the paraventricular, suprachiasmatic and dorsomedial nuclei of the hypothalamus. Exposing VSL rats to a short photoperiod regime (SPR; 06/18h light–dark cycle) for 21days ameliorated the anxiety-like behavior. VSL rats on SPR also exhibited increased food consumption and higher core body temperature. Our study supports the hypothesis that the ventral subiculum regulates anxiety-like behavior and that SPR helps in the alleviation of such behavior. Even though the mechanisms underlying anxiolytic effects of light–dark cycle manipulation are yet to be elucidated, such non-pharmacological strategies can help to mitigate anxiety-like behavior. A proper understanding of the effectiveness of photoperiod manipulation will help in developing strategies in the management of emotional disturbances associated with affective and neurodegenerative disorders including AD.

Distinct anxiogenic/anxiolytic effects exerted by the hamster lateral amygdalar nucleus injected with ORX-A or ORX-B in the presence of a GABAergic agonist.

Recently, there has been growing interest in the neurobiological role of some amygdalar neuromediators, such as GABA and orexins (ORX), that are responsible for stressful behaviors. Infusion of the major fear-related and panic-related basolateral amygdalar station, the lateral nucleus, with ORX-A and ORX-B, alone or in combination with the main α1-containing GABAA receptor agonist (zolpidem), modified anxiety states of the Syrian hamster. Single daily doses of ORX-A led to evident anxiogenic features, as pointed out by more time spent in the dark compartment of the light-dark exploration test, effects that were suppressed by zolpidem. Conversely, doses of ORX-B induced anxiolytic effects, whereas the concomitant administration of this neuropeptide with zolpidem strongly favored anxiogenic responses. In addition, these behavioral responses resulted in a widely correlated upregulation of the ORX-2 receptor in some key feeding and motor limbic areas, such as the ventromedial hypothalamic nucleus, central amygdalar nucleus, and hippocampal CA1 layer. Overall, these first indications on the differing anxiety states induced by ORX-A and ORX-B injected into the lateral amygdalar nucleus alone or in combination with zolpidem may constitute useful future therapeutic alternatives for the treatment of panic disorders as well as stressful behaviors.

Differential effects of subchronic Phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests

Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents.We addressed the question whether subchronic PCP (scPCP) treatment (5mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light–dark exploration test (LDT) and in an open field environment (OFT).The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity.Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.

Anxiolytic activity of methanol leaf extract of Achyranthes aspera Linn in mice using experimental models of anxiety

Objective:To study the anxiolytic activity of methanol extract of Achyranthes aspera Linn (Amaranthaceae).Materials and Methods:Male Swiss albino mice were used. Methanolic extract of Achyranthes aspera (MEAA) was administered in the doses of 100, 300 and 600 mg/kg p.o. Hole board (HB), open field (OF), elevated plus maze (EPM) and light/dark exploration (LDE) tests were used for determination of anxiolytic activity.Results:The methanolic extract of Achyranthes aspera significantly increased the number and duration of head poking in HB test. The extract also significantly increased the time spent and the number of entries in open arm in EPM. In LDE test, the extract produced significant increase in time spent and number of crossings and decreased the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearing, assisted rearing and the squares crossed.Conclusion:In the present study, MEAA exhibited anxiolytic activity which might be attributed to its phyto-constituents viz. alkaloid, steroid and triterpenes. Since Achyranthes aspera is ubiquitous and abundantly grown, it could be a fairly economical therapeutic agent for management of anxiety disorders.

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

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

A Study Of The Anxiolytic-Like Activity Of Dillenia Indica LINN. Leaves In Experimental Models Of Anxiety In Mice

:The purpose of this study was to characterize the putative anxiolytic-like activity of hydroethanolic extract prepared from the leaves of Dillenia indica . Materials and methods :Hydroethanolic extracts of Dillenia indica leaves at 50 ,100 and 200 mg/kg (p.o.) was adminsterd to study anxiolytic effect . Different models of anxiolytic activity viz. hole board , open field , elevated-plus maze and light/dark exploration models were used . Diazepam (2 mg/kg i.p.) was used as the standard drug . Observations : In the hole-board model , there was dose-dependent ( at 100 and 200 mg/kg) and significant (p<.05) increase in the number of headpokes and the time of head dipping in treated groups in comparison to vehicle . In open-field test , the number of rearing and squares traversed increased significantly (p<.05) at doses 100 and 200 mg/kg . In the elevated –plus maze , there was significant increase (p<.05) in time spent and number of entries into the openarms at doses of 100 and 200 mg/kg . In light-dark exploration test the extract at100 mg/kg and those at 200 mg/kg also showed significant activity (p<.05). Conclusion : Hydroethanolic extract of Dillenia indica leaves shows prominent anxiolytic activity in mice .

Levetiracetam-mediated emotional behavior in heterozygous rolling Nagoya Ca V2.1 channel mutant mice

Ca V2.1, which is highly expressed in the nervous system, plays an essential role in presynaptic neurotransmitter release. Although recent data suggest that the antiepileptic drug levetiracetam (LEV) inhibits presynaptic Ca V2.1 activity, the precise physiological role of Ca V2.1/LEV-regulated emotional performance has not been elucidated. We examined whether Ca V2.1/LEV mediates emotional behavior using a combined pharmacologic and genetic approach. Heterozygous rolling Nagoya ( rol/+) mice carrying the Ca V2.1α 1 mutation demonstrated normal emotional behavior. Exposure to 75 mg/kg LEV, which had no effect in wild-type controls, reduced anxiety in elevated plus maze and light–dark exploration tests and reduced depression in forced swimming and tail suspension behavioral tests in rol/+ mice. Similar behavioral patterns in motor activity were noted in wild-type and rol/+ mice injected with 0–150 mg/kg LEV. The phosphorylation of tryptophan hydroxylase at serine-58 and serotonin concentration were increased in the brainstems of rol/+ mice injected with 75 mg/kg LEV but not in those of wild-type controls. These results indicate that Ca V2.1/LEV mediates serotonin signaling leading to alterations in emotion. Our results also indicate that a combination of subthreshold pharmacologic and genetic approaches can be used to study functional signaling pathways in neuronal circuits.

Gestational exposure to the organophosphate chlorpyrifos alters social–emotional behaviour and impairs responsiveness to the serotonin transporter inhibitor fluvoxamine in mice

The organophosphate chlorpyrifos (CPF) is a pesticide largely used worldwide. Studies from animal models indicate that CPF exposure during development at low doses can target different neurotransmitter systems in the absence of overt cholinergic effects. Late gestational exposure (gestational days 14-17) to CPF at the dose of 6 mg/kg was evaluated in CD-1 mice at adulthood. Neurobehavioural effects likely involving serotonin (5-hydroxytryptamine, 5HT) transmission were assessed both in males and females, through the light-dark exploration test to assess CPF effects on anxiety profiles and the forced swimming test to evaluate the response to the 5HT transporter (5HTT) inhibitor fluvoxamine (30 mg/kg). In females only, we evaluated the effects of gestational exposure to CPF on maternal aggression, under basal condition or after injection of fluvoxamine. Gestational CPF exposure increased anxiety levels only in female mice, as shown by the augmented thigmotaxis behaviour and the lower latency to enter in the dark compartment. In the forced swimming test, no differences between CPF and control mice were found when assessed under basal condition (saline administration), but both male and female CPF mice missed to show the typical behavioural effects of the 5HTT inhibitor fluvoxamine. During maternal aggression, CPF females showed lower propensity to and intensity of aggressive behaviour, together with mild decreased responsiveness to fluvoxamine administration. Overall, the present results confirm a specific and sex-dependent vulnerability of affective/emotional domains to developmental CPF exposure. Furthermore, data provide clear indication on the disrupting effects of prenatal CPF on serotoninergic transmission.