Anxiety-like Behavior In Mice Research Articles

N6-substituated adenosine analog J4 attenuates anxiety-like behaviors in mice.

Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors. This study aimed to investigate the effects of J4 compared with saline using the mice vapor or voluntary ethanol drinking model on behavioral endpoints representing ethanol-withdrawal negative emotionality commonly observed during abstinence from chronic alcohol use. We subjected C57BL/6J mice to chronic intermittent ethanol (CIE) exposure schedule to investigate how 72-h withdrawal from alcohol alters affective-like behavior. Next, we determined how treatment with J4, a second-generation adenosine analog, influenced affective behaviors produced by alcohol withdrawal. Finally, we determined how J4 treatment alters voluntary ethanol drinking using the two-bottle-choice drinking paradigm. Our results show that 72-h withdrawal from chronic intermittent ethanol exposure produces limited affective-like disturbances in male C57BL/6J mice exposed to 4 cycles ethanol vapor. Most importantly, J4 treatment irrespective of ethanol exposure decreases innate anxiety-like behavior in mice. Withdrawal from chronic intermittent ethanol exposure and subsequent behavioral testing 72h later produces minimal affective-like behavior. J4 treatment did however reduce marble-burying behavior and increased time spent in open arms of the elevated plus maze, suggesting J4 may be useful as a general anxiolytic.

Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice

Despite the prevalence of anxiety disorders, the molecular identity of neural circuits underlying anxiety remains unclear. The lateral hypothalamus (LH) is one brain region implicated in the regulation of anxiety, and our recent data found that chemogenetic activation of LH galanin neurons attenuated the stress response to a novel environment as measured by the marble burying test. Thus, we hypothesize that LH galanin neurons may contribute to anxiety-related behavior. We used chemogenetics and fiber photometry to test the ability of LH galanin neurons to influence anxiety and stress-related behavior. Chemogenetic activation of LH galanin neurons significantly decreased anxiety-like behavior in the elevated plus maze, open field test, and light dark test. However, LH galanin activation did not alter restraint stress induced HPA activation or freezing behavior in the fear conditioning paradigm. In vivo calcium monitoring by fiber photometry indicated that LH galanin neurons were activated by anxiogenic and/or stressful stimuli including tail suspension, novel mouse interaction, and predator odor. Further, in a fear conditioning task, calcium transients strongly increased during foot shock, but were not affected by the unconditioned stimulus tone. These data indicate that LH galanin neurons both respond to and modulate anxiety, with no influence on stress induced HPA activation or fear behaviors. Further investigation of LH galanin circuitry and functional mediators of behavioral output may offer a more refined pharmacological target as an alternative to first-line broad pharmacotherapies such as benzodiazepines.

Distinct Hypothalamic Paraventricular Nucleus Inputs to the Cingulate Cortex and Paraventricular Thalamic Nucleus Modulate Anxiety and Arousal.

Insomnia and anxiety are two common clinical diseases that threaten people’s physical and mental health. Insomnia and anxiety may share some similar underlying neural circuit mechanisms in the brain. In this study, we combine techniques including chemo-fMRI, optogenetics, and chemogenetics to reveal that the glutamatergic neurons of the paraventricular hypothalamic nucleus (PVN) regulate both anxiety and arousal through two different downstream neural circuits. Optogenetic activation of the PVN-cingulate cortex (Cg) neural circuit triggers anxiety-like behaviors in mice without affecting the wakefulness, while optogenetic activation of the PVN-paraventricular thalamic nucleus (PVT) neural circuit promotes wakefulness in mice without affecting anxiety-like behaviors. Our research reveals that PVN is a key brain area for controlling anxiety and arousal behaviors. We also provide a neurological explanation for anxiety disorder and insomnia which may offer guidance for treatments including drugs or transcranial magnetic stimulation for the patients.

Blast-Induced Mild Traumatic Brain Injury Alterations of Corticotropin-Releasing Factor Neuronal Activity in the Mouse Hypothalamic Paraventricular Nucleus.

Blast-induced mild traumatic brain injury (mbTBI) is the most common cause of TBI in US service members and veterans. Those exposed to TBI are at greater risk of developing neuropsychiatric disorders such as posttraumatic stress disorder, anxiety and depressive disorders, and substance use disorders following TBI. Previously, we have demonstrated that mbTBI increases anxiety-like behaviors in mice and dysregulates stress at the level of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN). To expand on how mTBI may dysregulate the stress axis centrally, here PVN CRF neuronal activity was evaluated using whole cell-patch clamp recordings in hypothalamic slices from sham and mbTBI adult male CRF:tdTomato mice 7 days post-injury. We found that mbTBI generally did not affect the neuronal excitability and intrinsic membrane properties of PVN CRF neurons; this injury selectively increased the frequency of spontaneous neuronal firing of PVN CRF neurons localized to the dorsal PVN (dPVN) but not ventral PVN (vPVN). Consistently, mbTBI-induced dPVN CRF hyperactivity was associated with pre- and post-synaptic depression of spontaneous GABAergic transmission onto dPVN CRF neurons suggesting that mbTBI-induced GABAergic synaptic dysfunction may underlie dPVN CRF neuronal hyperactivity and increases in dPVN CRF signaling. The present results provide the first evidence for mbTBI-induced alterations in PVN CRF neuronal activity and GABAergic synaptic function that could mediate hypothalamic CRF dysregulation following mbTBI contributing to stress psychopathology associated with blast injury.

Innate immune stimulation prevents the development of anxiety-like behaviors in chronically stressed mice

Anxiety is a common psychological disease which can induce severe social burdens. Searching methods that prevent the onset of anxiety is of great significance for ameliorating the social and individual problems induced by this type of disease. In this study, we investigated how innate immune pre-stimulation influences the anxiety-like behaviors in chronically stressed mice. Our results showed that a single injection of an innate immune stimulant lipopolysaccharide (LPS) at the dose of 50, 100, and 500 μg/kg 1 day before stress exposure prevented chronic social defeat stress (CSDS)-induced anxiety-like behaviors in mice. A single injection of LPS (100 μg/kg) 5 days before stress exposure produced similar preventive effects on CSDS-induced anxiety-like behaviors, while similar effects were not observed at the condition of 10-days interval between LPS injection and stress exposure. A second LPS injection 10 days after the first LPS injection or a 4 × LPS injection 10 days before stress exposure also prevented CSDS-induced anxiety-like behaviors. Moreover, a single injection of LPS (100 μg/kg) 1 day before stress exposure prevented the production of pro-inflammatory cytokines in the hippocampus and prefrontal cortex of CSDS mice. Suppression of innate immune stimulation by minocycline pretreatment simultaneously abrogated the preventive effect of LPS pre-injection (100 μg/kg) on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine production in the brain. Our results demonstrated that the pre-stimulation of the innate immune system can prevent the development of anxiety-like behaviors and the progression of the neuroinflammatory responses in the brain in chronically stressed mice.This article is part of the special Issue on ‘Stress, Addiction and Plasticity'.

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice.

Individuals suffering from mood and anxiety disorders often show significant disturbances in sleep and circadian rhythms. Animal studies indicate that circadian rhythm disruption can cause increased depressive- and anxiety-like behavior, but the underlying mechanisms are unclear. One potential mechanism to explain how circadian rhythms are contributing to mood and anxiety disorders is through dysregulation of the suprachiasmatic nucleus (SCN) of the hypothalamus, known as the “central pacemaker.” To investigate the role of the SCN in regulating depressive- and anxiety-like behavior in mice, we chronically manipulated the neural activity of the SCN using two optogenetic stimulation paradigms. As expected, chronic stimulation of the SCN late in the active phase (circadian time 21, CT21) resulted in a shortened period and dampened amplitude of homecage activity rhythms. We also repeatedly stimulated the SCN at unpredictable times during the active phase of mice when SCN firing rates are normally low. This resulted in dampened, fragmented, and unstable homecage activity rhythms. In both chronic SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) were directly correlated with increased measures of anxiety-like behavior. In contrast, we only observed a correlation between behavioral despair and homecage activity amplitude in mice stimulated at CT21. Surprisingly, the change in period of homecage activity rhythms was not directly associated with anxiety- or depressive-like behavior. Finally, to determine if anxiety-like behavior is affected during a single SCN stimulation session, we acutely stimulated the SCN in the active phase (zeitgeber time 14-16, ZT14-16) during behavioral testing. Unexpectedly this also resulted in increased anxiety-like behavior. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like behavior. This work is an important step in understanding how specific SCN neural activity disruptions affect depressive- and anxiety-related behavior.

Innate immune stimulation by monophosphoryl lipid A prevents chronic social defeat stress-induced anxiety-like behaviors in mice

BackgroundInnate immune pre-stimulation can prevent the development of depression-like behaviors in chronically stressed mice; however, whether the same stimulation prevents the development of anxiety-like behaviors in animals remains unclear. We addressed this issue using monophosphoryl lipid A (MPL), a derivative of lipopolysaccharide (LPS) that lacks undesirable properties of LPS but still keeps immune-enhancing activities.MethodsThe experimental mice were pre-injected intraperitoneally with MPL before stress exposure. Depression was induced through chronic social defeat stress (CSDS). Behavioral tests were conducted to identify anxiety-like behaviors. Real-time polymerase chain reaction (PCR) and biochemical assays were employed to examine the gene and protein expression levels of pro-inflammatory markers.ResultsA single MPL injection at the dose of 400 and 800 μg/kg 1 day before stress exposure prevented CSDS-induced anxiety-like behaviors, and a single MPL injection (400 μg/kg) five but not 10 days before stress exposure produced similar effect. The preventive effect of MPL on anxiety-like behaviors was also observed in CSDS mice who received a second MPL injection 10 days after the first MPL injection or a 4 × MPL injection 10 days before stress exposure. MPL pre-injection also prevented the production of pro-inflammatory cytokines in the hippocampus and medial prefrontal cortex in CSDS mice, and inhibiting the central immune response by minocycline pretreatment abrogated the preventive effect of MPL on CSDS-induced anxiety-like behaviors and pro-inflammatory cytokine productions in the brain.ConclusionsPre-stimulation of the innate immune system by MPL can prevent chronic stress-induced anxiety-like behaviors and neuroinflammatory responses in the brain in mice.

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments.

Mild traumatic brain injury induced by low-intensity blast (LIB) exposure poses concerns in military personnel. Using an open-field, non-inertial blast model and assessments by conventional behavioral tests, our previous studies revealed early-phase anxiety-like behaviors in LIB-exposed mice. However, the impact of LIB upon long-term anxiety-like behaviors requires clarification. This study applied a highly sensitive automated home-cage monitoring (HCM) system, which minimized human intervention and environmental changes, to assess anxiety-like responses in mice 3 months after LIB exposure. Initial assessment of 72-h spontaneous activities in a natural cage condition over multiple light and dark phases showed altered sheltering behaviors. LIB-exposed mice exhibited a subtle, but significantly decreased, duration of short shelter visits as compared to sham controls. Other measured responses between LIB-exposed mice and sham controls were insignificant. When behavioral assessments were performed in a challenged condition using an aversive spotlight, LIB-exposed mice demonstrated a significantly higher frequency of movements of shorter distance and duration per movement. Taken together, these findings demonstrated the presence of chronic anxiety-like behaviors assessed by the HCM system under both natural and challenged conditions in mice occurring post-LIB exposure. This model thus provides a platform to test for screening and interventions on anxiety disorders occurring after LIB non-inertial brain injury.

Assessment of general activity and anxietylike behavior in mice following tramadol and meloxicam administration for managing immediate post-operative pain

Assessment of general activity and anxietylike behavior in mice following tramadol and meloxicam administration for managing immediate post-operative pain

Dexmedetomidine Alleviates Anxiety-Like Behavior in Mice Following Peripheral Nerve Injury by Reducing the Hyperactivity of Glutamatergic Neurons in the Anterior Cingulate Cortex

Dexmedetomidine Alleviates Anxiety-Like Behavior in Mice Following Peripheral Nerve Injury by Reducing the Hyperactivity of Glutamatergic Neurons in the Anterior Cingulate Cortex

The L-DOPA receptor GPR143 in the indirect pathways regulates an anxiety-like behavior in mice

The L-DOPA receptor GPR143 in the indirect pathways regulates an anxiety-like behavior in mice

Apple phenolic extracts ameliorate lead-induced cognitive impairment and depression- and anxiety-like behavior in mice by abating oxidative stress, inflammation and apoptosis via the miR-22-3p/SIRT1 axis.

Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.

Alpha2-antiplasmin deficiency affects depression and anxiety-like behavior and apoptosis induced by stress in mice.

Depression is a psychiatric disorder that affects about 10% of the world's population and is accompanied by anxiety. Depression and anxiety are often caused by various stresses. However, the etiology of depression and anxiety remains unknown. It has been reported that alpha2-antiplasmin (α2AP) not only inhibits plasmin but also has various functions such as cytokine production and cell growth. This study aimed to determine the roles of α2AP on the stress-induced depression and anxiety. We investigated the mild repeated restraint stress-induced depressive and anxiety-like behavior in the α2AP+/+ and α2AP-/- mice using the social interaction test (SIT), sucrose preference test (SPT), and elevated plus maze (EPM). The stresses such as the mild repeated restraint stress suppressed α2AP expression in the hippocampus of mice, and the treatment of fluoxetine (selective serotonin reuptake inhibitor [SSRI]) recovered the stress-caused α2AP suppression. We also showed that α2AP deficiency promoted the mild restraint stress-stimulated depression-like behavior such as social withdrawal and apathy and apoptosis in mice. In contrast, α2AP deficiency attenuated the mild restraint stress induced the anxiety-like behavior in mice. α2AP affects the pathogenesis of depression and anxiety induced by stress.

TNF signaling pathway-mediated microglial activation in the PFC underlies acute paradoxical sleep deprivation-induced anxiety-like behaviors in mice

Acute sleep deprivation is a common condition in modern life and increases anxiety symptoms in healthy individuals. The neuroinflammatory response induced by microglial activation could be an important contributing factor, but its underlying molecular mechanisms are still unclear. In the present study, we first found that acute paradoxical sleep deprivation (PSD) induced by the modified multiple platform method (MMPM) for 6 h led to anxiety-like behavior in mice, as verified by the open field test, elevated plus maze test, light–dark box test, and marble burying test. In addition, bioinformatic analysis suggested an important relationship between acute sleep deprivation and brain inflammatory signaling pathways. Key genes enriched in the TNF signaling pathway were confirmed to be altered during acute PSD by qPCR and Western blot analyses, including the upregulation of the prostaglandin-endoperoxide synthase 2 (Ptgs2) and suppressor of cytokine signaling 3 protein (Socs3) genes and the downregulation of the cysteine-aspartic acid protease 3 (Casp3) gene. Furthermore, we found that microglial cells in the prefrontal cortex (PFC) were activated with significant branch structure changes and that the cell body area was increased in the PSD model. Finally, we found that minocycline, a tetracycline with anti-inflammatory properties, may ameliorate the anxiogenic effect and microglial activation. Our study reveals significant correlations of anxiety-like behavior, microglial activation, and inflammation during acute PSD.

High fat diet-induced obesity leads to depressive and anxiety-like behaviors in mice via AMPK/mTOR-mediated autophagy

Depression is one of the most common mental illnesses in modern society. In recent years, several studies show that there are disturbances in lipid metabolism in depressed patients. High-fat diet may lead to anxiety and depression, but the mechanisms involved remain unclear. In our study, we found that 8 weeks of high-fat feeding effectively induced metabolic disorders, including obesity and hyperlipidemia in mice. Interestingly, the mice also showed depressive and anxiety-like behaviors. We further found activated microglia and astrocyte, increased neuroinflammation, decreased autophagy and BDNF levels in mice after high-fat feeding. Besides, high-fat feeding can also inhibit AMPK phosphorylation and induce mTOR phosphorylation. After treating with the mTOR inhibitor rapamycin, autophagy and BDNF levels were elevated. The number of activated microglia and astrocyte, and pro-inflammation levels were reduced. Besides, rapamycin can also reduce the body weight and serum lipid level in high fat feeding mice. Depressive and anxiety-like behaviors were also ameliorated to some extent after rapamycin treatment. In summary, these results suggest that high-fat diet-induced obesity may lead to depressive and anxiety-like behaviors in mice by inhibiting AMPK phosphorylation and promoting mTOR shift to phosphorylation to inhibit autophagy. Therefore, improving lipid metabolism or enhancing autophagy through the AMPK/mTOR pathway could be potential targets for the treatment of obesity depression.

Exposure to single prolonged stress fails to induce anxiety-like behavior in mice

Single prolonged stress (SPS) is a well-established and most frequently used rat model to induce post-traumatic stress disorder (PTSD)-like symptoms, which helps to understand the neurobiological mechanisms as well as developing novel therapeutic strategies for PTSD. However, whether such stress model works efficiently in mice remains unknown. In the present study, we established a mouse SPS (mSPS) model by exposing C57BL/6J mice to a series of multimodal stressors on a single day, then the anxiety-like behavior was measured by open-field test, elevated plus maze test, dark-light box, and novelty-suppressed feeding test. Our results showed that mSPS had no significant effect on the anxiety-like behavior in mice after different days of recovery. The expression of the glucocorticoid receptor and brain-derived neurotrophic factor (BDNF), two proteins that highly associated with stress-related behaviors, also remained unaltered in both the amygdala and hippocampus. By contrast, the protein levels of NR2A and NR2B, two main subunits of the <i>N</i>-methyl-D-aspartate receptor (NMDAR), was reduced in the hippocampus, but not amygdala. In conclusion, our results indicate that mSPS may not be an efficient mouse model to explore the pathophysiology of PTSD-related anxiety-like behavior.

The Effect of Serotonin-Norepinephrine Reuptake Inhibitor Milnacipran on Anxiety-like Behaviors in Diabetic Mice

Background: Diabetes mellitus is a chronic disease that causes neuronal plasticity and increased hypothalamic pituitary adrenal (HPA) axis of stress disorders. The change in metabolism is reportedly associated with inadequate response to antianxiety and antidepressant agents. Objective: This study aimed to determine the effect of milnacipran antidepressants on anxiety-like behavior in mice with diabetes mellitus. Methods: Male ICR mice were divided into naive, stress, diabetes mellitus (DM), DM + stress groups to measure anxiety-like behavior. Diabetes mellitus was induced using alloxan, and electric footshock stress was used as a stressor for 14 consecutive days. Anxiety-like behavior was measured using the light-dark box (LDB) and elevated plus maze (EPM) test at days 0, 7 and 14. The antidepressant milnacipran (MIL) was given for 7 days, on days 8 to 14. On day 14, evaluation of anxiety-like behavior after administration of MIL was carried out in all groups using LDB and EPM tests. Results: The results showed that administration of milnacipran effectively ameliorated anxiety-like behavior in the non-DM, but not in the DM group, using the LDB test. A similar result was demonstrated in the EPM test showing the non-DM group's attenuation after milnacipran administration. Conclusion: The present results indicate that there is an inadequate attenuation of the anxiety-like behavior after treatment with milnacipran in diabetes conditions.

Exogenous Carbon Monoxide Produces Rapid Antidepressant- and Anxiolytic-Like Effects.

Carbon monoxide (CO), a byproduct of heme catalyzed by heme oxygenase (HO), has been reported to exert antioxidant and anti-inflammatory actions, and to produce significant neuroprotective effects. The potential effects of CO and even HO on depressive-like behaviors are still poorly understood. Utilizing several approaches including adeno-associated virus (AAV)-mediated overexpression of HO-1, systemic CO-releasing molecules (CO-RMs), CO-rich saline or CO gas treatment procedures in combination with hydrogen peroxide (H2O2)-induced PC12 cell injury model, and lipopolysaccharide (LPS)-induced depression mouse model, the present study aimed to investigate the potential antidepressant- and anxiolytic-like effects of endogenous and exogenous CO administration in vivo and in vitro. The results of in vitro experiments showed that both CO-RM-3 and CO-RM-A1 pretreatment blocked H2O2-induced cellular injuries by increasing cell survival and decreasing cell apoptosis and necrosis. Similar to the effects of CO-RM-3 and CO-RM-A1 pretreatment, AAV-mediated HO-1 overexpression in the dorsal hippocampus produced significant antidepressant-like activities in mice under normal conditions. Further investigation showed that the CO gas treatment significantly blocked LPS-induced depressive- and anxiety-like behaviors in mice. Taken together, our results suggest that the activation of HO-1 and/or exogenous CO administration produces protective effects and exerts antidepressant- and anxiolytic-like effects. These data uncover a novel function of the HO-1/CO system that appears to be a promising therapeutic target for the treatment of depression and anxiety.

Curcumin Ameliorates the Cd-Induced Anxiety-like Behavior in Mice by Regulating Oxidative Stress and Neuro-Inflammatory Proteins in the Prefrontal Cortex Region of the Brain.

Age-related neurodegenerative diseases and vascular dementia are major challenges to the modern health care system. Most neurodegenerative diseases are associated with impaired spatial working memory and anxiety-like behavior. Thus, it is important to understand the underlying cellular mechanisms of neurodegenerative diseases in different regions of the brain to develop an effective therapeutic approach. In our previous research paper, we have reported the ameliorative effect of curcumin in Cd-induced hippocampal neurodegeneration. However, recently many researchers had reported the important role of the prefrontal cortex in higher cognitive functions. Therefore, to look into the cellular mechanism of curcumin protection against Cd-induced prefrontal cortex neurotoxicity, we investigated spatial working memory, anxiety-like behavior and analyzed prefrontal cortex inflammatory markers (IL-6, IL-10, and TNFα), antioxidant enzymes (SOD, GSH, and CAT), and pro-oxidant MDA level. Further, we conducted histological studies of the prefrontal cortex in Swiss albino mice exposed to cadmium (2.5 mg/kg). We observed that curcumin treatment improved the spatial working memory and anxiety-like behavior of mice through reduction of prefrontal cortex neuroinflammation and oxidative stress as well as increasing the number of viable prefrontal cortex neuronal cells. Our result suggests that environmental heavy metal cadmium can induce behavioral impairment in mice through prefrontal cortex cellular inflammation and oxidative stress. We found that curcumin has a potential therapeutic property to mitigate these behavioral and biochemical impairments induced by cadmium.

Pharmacological investigations of neuroprotective potential of Centella lujica supplement on sleep deprivation-induced anxiety-like behaviour in mice

Background: Sleep deprivation has often been implicated in several neurological disorders. Centella lujica is a psychoactive herb with medically-beneficial therapeutic potential. The current study sought to evaluate the neuroprotective effect of Centella lujica supplement in experimental animals.Methods: Sleep deprivation in mice was done using the multiple platforms over water model.Results: Upon treatment with Centella lujica supplement, the parameters of anxiety-like behaviour induced by sleep deprivation were found to be significantly diminished in comparison to the sleep deprived animals.Conclusions: Centella lujica treatment significantly decreased hyper locomotion, and anxiety-like behaviour caused by sleep deprivation.