Percentage Of Open Arm Entries Research Articles

An Alternative Analysis of Computational Learning within Behavioral Neuropharmacology in an Experimental Anxiety Model Investigation

Behavioral neuropharmacology, a branch of neuroscience, uses behavioral analysis to demonstrate treatment effects on animal models, which is fundamental for pre-clinical evaluation. Typically, this determination is univariate, neglecting the relevant associations for understanding treatment effects in animals and humans. This study implements regression trees and Bayesian networks from a multivariate perspective by using variables obtained from behavioral tests to predict the time spent in the open arms of the elevated arm maze, a key variable to assess anxiety. Three doses of allopregnanolone were analyzed and compared to a vehicle group and a diazepam-positive control. Regression trees identified cut-off points between the anxiolytic and anxiogenic effects, with the anxiety index standing out as a robust predictor, combined with the percentage of open-arm entries and the number of entries. Bayesian networks facilitated the visualization and understanding of the interactions between multiple behavioral and biological variables, demonstrating that treatment with allopregnanolone (2 mg) emulates the effects of diazepam, validating the multivariate approach. The results highlight the relevance of integrating advanced methods, such as Bayesian networks, into preclinical research to enrich the interpretation of complex behavioral data in animal models, which can hardly be observed with univariate statistics.

Anxiolytic effects of Dichrocephala integrifolia leaf aqueous extract on alcohol withdrawal-induced anxiety in mice: Involvement of the GABAergic pathway

Ethanol withdrawal syndrome is a life-threatening state that results from a sudden termination of chronic alcohol intake. One of the manifestations of ethanol withdrawal syndrome is anxiety. Dichrocephala integrifolia is a plant used in Africa in the treatment of alcohol use disorders. This study aimed to evaluate the effects of Dichrocephala integrifolia on ethanol withdrawal anxiety in mice. Young adult Swiss mice were arranged into seven groups of six mice each. Groups II to VII received ethanol in increasing concentration for 20 days. Following ethanol withdrawal, mice were administered distilled water (Group II), Dichrocephala integrifolia (25,50,100 and 200 mg/kg) (Groups III-VI) or diazepam (Group VII). Behavioural assessments were performed using the elevated plus maze, the open field and the hole board tests. Gamma-aminobutyric acid (GABA) concentration, GABA-Transaminase and glutamic acid decarboxylase activities were assessed in the brain. In the elevated plus maze, Dichrocephala integrifolia (100 mg/kg) significantly (p < 0.01) increased the percentage of open arms entries from 20.5 ± 1.56% in the negative control, to 65.3 ± 2.46%. In the hole board, the number of head dipping raised from 27.17 ± 0.60 in the negative control to 61.33 ± 2.82 (p < 0 0.01) at the dose 200 mg/kg of Dichrocephala integrifolia. Likewise, diazepam, Dichrocephala integrifolia (200 mg/kg) significantly (p < 0.01) raised GABA concentration from 267.70 ± 5.18 µg/g of tissue in the negative control to 395 ± 5.55 µg/g of tissue. The plant extract (200 mg/kg) reduced the activity of GABA-Transaminase from 101 ± 2.60 pg/min/mg of tissue in the negative control to 42.5 ± 2.35 pg/min/mg of tissue. From these results, we can conclude that, by enhancing the GABAergic neurotransmission, Dichrocephala integrifolia has anxiolytic activities against ethanol withdrawal anxiety and can therefore be a good drug candidate for the treatment of alcohol addiction.

Therapeutic potential of Anacyclus pyrethrum aqueous extract in managing Clonazepam withdrawal in rats

The management of benzodiazepine withdrawal syndrome is challenging, and there is currently no consensus on the optimal treatment approach. Our study aims to investigate the possible effect of the aqueous extract of Anacyclus pyrethrum (AEAP) on Clonazepam dependence in rats via the measurement of oxidative stress, behavioral and biochemical changes. Dependence was induced by chronic administration of Clonazepam for 30 days, then AEAP was administered orally to rats. Withdrawal syndrome was assessed employing the conditioned place preference test, behavioral tests, and biochemical assays. Oxidative stress was evaluated by measuring levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD). The percentage of open-arm entries, time spent in open arms decreased, and immobility time increased significantly among the Clonazepam-dependent group from the preconditioning to withdrawal phase (p &lt; 0.001). The cortisol level was higher among Clonazepam group, the MDA increased, and CAT and SOD measurements demonstrated a notable decrease in the Clonazepam withdrawal group. AEAP administration at a dose of 200 mg/kg significantly alleviated anxiety and depression-like behaviors and led to a substantial decrease in oxidative stress levels during Clonazepam withdrawal, demonstrating the beneficial impact of AEAP. The use of Anacyclus pyrethrum may provide a novel therapeutic approach for managing the adverse effects of Clonazepam dependence by targeting oxidative stress.

Effect of Echinacea Purpurea Extract on Anxiety-Like Behaviors in Neonatal Rats

Background: The use of herbal products is increased among people wordwide. Regarding lacking evidence on the use of herbal medication in children, this study was aimed to determine the effects of Echinacea Purpurea extract on anxiety-like behavior in neonatal rats. Materials and Methods: Forty male Wister strain pups in four groups received i.p injections of E. Purpurea extract (40, 80, and 250 mg/kg) or saline on 5th to 9th postnatal days. All pups were examined for anxiety test on the 22nd postnatal day in the elevated plus-maze test. During the test, parameters include percentage of open arm time (%OAT), percentage of open arm entry (%OAE), head dipping, rearing and locomotor activity have been measured. Results: In the present study, administration of 40, 80 and 250mg/kg doses of the E. Purpurea extract revealed a significant decrease in the %OAT compared to saline group (P&lt;0.01). The E. Purpurea extract decreased head dipping parameters (P&lt;0.01) and increased rearing parameters (P&lt;0.01). E. Purpurea did not significantly change the locomotor activity. Conclusions: The results of present study showed that postnatal administration of E. Purpurea extract increases anxiety in neonatal rats comparing to control group. [GMJ.2017;6(1):52-60]

Comparative effects of the alcoholic extract of Terminalia chebula and crocin on stress‑induced anxiety‑like behavior and memory impairment in male rats.

Crocin and Terminalia chebula (T. chebula) were proven to have neuroprotective effects. In this study, we evaluated the preventive effects of crocin and alcoholic extract of the T. chebula alone and in combination to examine their efficacy against chronic restraint stress (CRS)‑induced cognitive impairment, anxiety‑like behaviors, hippocampal synaptic plasticity deficit as well as neuronal arborization damage in the hippocampal CA1 neurons. Over 14 consecutive days, animals received crocin, T. chebula, or their combination (5 min before CRS). The elevated plus‑maze results showed that crocin and T. chebula alone and in combination treatment significantly increased the time spent in open arms, percentage of open arm entries, and head dipping as compared with the CRS group. Barnes maze results showed that administration of crocin and T. chebula alone and their combination significantly improves spatial memory indicators such as distance traveled, latency time to achieving the target hole, and the number of errors when compared to the CRS group. These learning deficits in CRS animals correlated with a reduction of long-term potentiation (LTP) in hippocampal CA1 synapses, which both T. chebula and crocin treatment improved field excitatory postsynaptic potentials (fEPSP) amplitude and fEPSP slope reduction induced by CRS. Golgi‑Cox staining showed that T. chebula and crocin treatment increased the number of dendrites and soma arbors in the CA1 neurons compared with the CRS group. Our results suggest that both T. chebula and crocin attenuated CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons. We found no significant difference between single treatments of T. chebula or crocin and their combination in protecting CRS‑induced anxiety‑like behaviors, memory impairment, and synaptic plasticity loss in hippocampal CA1 neurons.

Behavioral effects induced by the cannabidiol analogs HU-502 and HU-556.

Cannabidiol is a phytocannabinoid that lacks the psychotomimetic properties of Δ9-tetrahydrocannabinol (THC), the main psychoactive Cannabis sativa component. Cannabidiol has several potential therapeutic properties, including anxiolytic, antidepressant, and antipsychotic; however, cannabidiol has low oral bioavailability, which can limit its clinical use. Here, we investigated if two cannabidiol analogs, HU-502 and HU-556, would be more potent than cannabidiol in behavioral tests predictive of anxiolytic, antidepressant, and antipsychotic effects. Different doses (0.01-3 mg/kg; intraperitoneally) of HU-556 and HU-502 were tested in male Swiss mice submitted to the elevated plus maze (EPM), forced swimming test (FST), and amphetamine-induced-prepulse inhibition (PPI) disruption and hyperlocomotion. Cannabidiol is effective in these tests at a dose range of 15-60 mg/kg in mice. We also investigated if higher doses of HU-556 (3 and 10 mg/kg) and HU-502 (10 mg/kg) produced the cannabinoid tetrad (hypolocomotion, catalepsy, hypothermia, and analgesia), which is induced by THC-like compounds. HU-556 (0.1 and 1 mg/kg) increased the percentage of open arm entries (but not time) in the EPM, decreased immobility time in the FST, and attenuated amphetamine-induced PPI disruption. HU-502 (1 and 3 mg/kg) decreased amphetamine-induced hyperlocomotion and PPI impairment. HU-556, at high doses, caused catalepsy and hypolocomotion, while HU-502 did not. These findings suggest that similar to cannabidiol, HU-556 could induce anxiolytic, antidepressant, and antipsychotic-like effects and that HU-502 has antipsychotic properties. These effects were found at a dose range devoid of cannabinoid tetrad effects.

Hesperidin Exerts Anxiolytic-like Effects in Rats with Streptozotocin- Induced Diabetes via PKA/CREB Signaling.

The mechanisms underlying synaptic injury and anxiety-like behavioral changes caused by diabetes and the strategies to reverse these changes are not well understood. This study examined the neuroprotective effects of hesperidin on anxiety-like behaviors in diabetic rats and investigated the underlying mechanisms from the perspective of the PKA/CREB pathway. Rats with streptozotocin-induced diabetes were treated orally with hesperidin (50 and 150 mg/kg) for 10 weeks. The elevated plus maze (EPM), hole board test (HBT), and marbleburying test (MBT) were used to assess anxiety-like behaviors. We further examined the effects of hesperidin on the PKA/CREB pathway in vivo and in vitro. The results show that supplementation with hesperidin exerted anxiolytic effects on the diabetic rats, as evidenced by increased percentages of open arm entries and time spent in the open arms in the EPM; decreased numbers of hole visits in the HBT; decreased numbers of marbles buried; and increased expression of PKA, CREB, BDNF, and synaptic proteins in the amygdala and hippocampus of diabetic rats. Hesperidin was found to reverse the imbalance in the PKA/CREB/BDNF pathway. In vitro, we found that the PKA inhibitor H89 reversed the protective effects of hesperidin against cell injury and reversed the HG-induced expression of PKA, pCREB/CREB, and BDNF. Our results demonstrated that hesperidin could ameliorate the anxiety-like behaviors of diabetic rats and that activating the PKA/CREB/BDNF pathway contributed to the beneficial effects. This study may provide important insights into the mechanisms underlying anxiety-like behaviors in diabetes and identify new therapeutic targets for clinical treatment.

Mifepristone blocks the anxiolytic- and antidepressant-like effects of allopregnanolone in male rats

Background Allopregnanolone (3α, 5α-tetrahydroprogesterone) is an inhibitory neurosteroid synthesized from progesterone via 5α-reductase activity in the brain and has anxiolytic, antidepressant, sedative, anticonvulsant, and analgesic activity. Altered levels of allopregnanolone cause anxiety, depression, premenstrual syndrome, and psychiatric disorders. Although allopregnanolone exerts most of its actions by modulating GABAA receptor, NMDA receptor, BDNF expression, and PXR activity, a recent study showed its effects are blocked by mifepristone on lordosis behavior which indicates the involvement of progestin or glucocorticoid receptors in the effects of allopregnanolone since mifepristone blocks both these receptors. However, whether these receptors are involved in acute anxiolytic or antidepressant-like effects is unknown. Methods Adult male Wistar rats were used to study whether the prior administration of mifepristone would alter the effects of allopregnanolone in the elevated plus maze (EPM) and forced swim test (FST) was evaluated. Results 10 mg/Kg dose of allopregnanolone increased percent open arm entries in the EPM, whereas 3 mg/Kg dose of allopregnanolone decreased percent immobility in the FST. Mifepristone administration resulted in a U-shaped response in the FST (with 1 mg/Kg, s.c., decreasing the immobility time) without significantly impacting the behavior in the EPM. In combination studies, mifepristone blocked the anxiolytic and antidepressant effects of allopregnanolone. Conclusion The current study provides evidence for the first time that progestin or glucocorticoid receptors are involved in the acute anxiolytic and antidepressant effects of allopregnanolone. Understanding the mechanism of action of allopregnanolone will help us design better therapeutic strategies to treat neuropsychiatric diseases such as depression and anxiety.

Oxycodone decreases anxiety-like behavior in the elevated plus-maze test in male and female rats.

The prescription opioid oxycodone is widely used for the treatment of pain in humans. Oxycodone misuse is more common among people with an anxiety disorder than those without one. Therefore, oxycodone might be misused for its anxiolytic properties. We investigated if oxycodone affects anxiety-like behavior in adult male and female rats. The rats were treated with oxycodone (0.178, 0.32, 0.56, or 1 mg/kg), and anxiety-like behavior was investigated in the elevated plus-maze test. Immediately after the elevated plus-maze test, a small open field test was conducted to determine the effects of oxycodone on locomotor activity. In the elevated plus-maze test, oxycodone increased the percentage of time spent on the open arms, the percentage of open arm entries, time on the open arms, open arm entries, and the distance traveled. The males treated with vehicle had a lower percentage of open arm entries than the females treated with vehicle, and oxycodone treatment led to a greater increase in the percentage of open arm entries in the males than females. Furthermore, the females spent more time on the open arms, made more open arm entries, spent less time in the closed arms, and traveled a greater distance than the males. In the small open field test, treatment with oxycodone did not affect locomotor activity or rearing. Sex differences were observed; the females traveled a greater distance and displayed more rearing than the males. In conclusion, oxycodone decreases anxiety-like behavior in rats, and oxycodone has a greater anxiolytic-like effect in males than females.

Mesenchymal stem cells and their conditioned medium as potential therapeutic strategies in managing comorbid anxiety in rat sepsis induced by cecal ligation and puncture.

Objective(s):Sepsis-associated encephalopathy (SAE) is a common brain dysfunction following sepsis. Due to the beneficial effects of mesenchymal stem cells (MSCs) therapy on anxiety, an extreme and early manifestation of SAE, we hypothesized that MSCs-derived conditioned medium (CM) may be able to attenuate anxiety in cecal ligation and puncture (CLP)-induced sepsis.Materials and Methods:Rats were assigned into 4 groups: sham, CLP, MSC, and CM. All animals, except in the sham group, underwent the CLP procedure to induce sepsis. Two hours after sepsis induction, the rats in MSC and CM groups, received 1×106 MSCs and CM derived from the same number of cells, respectively. 48 hr after the treatments, anxiety-related behaviors were assessed, and brain and right hippocampal tissues were collected.Results:MSCs and CM enhanced the percentages of open arm entries and time spent in the open arms of the elevated plus-maze and the time spent in the light side of the light-dark box. MSCs and CM decreased the Evans blue content and decreased the IL-6 and TNF-α levels in the brain tissue samples. Reductions in the expression of 5-HT2A receptors and phosphorylation of ERK1/2 and an increase in the expression of 5-HT1A receptors in the hippocampal tissue samples were observed in the MSC and CM groups.Conclusion:MSCs and MSCs-derived CM attenuated anxiety-related behaviors to an equal extent by reducing inflammation, modifying 5-HT receptor expression changes, and inhibiting the ERK pathway. Therefore, MSCs-derived CM may be considered a promising therapy for comorbid anxiety in septic patients.

Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson's disease induced by paraquat

Objective: To observe the intestinal time-dependent changes in Parkinson's disease (PD) mouse model constructed by intraperitoneal injection of paraquat (PQ) and to establish the brain-gut axis connection initially. Methods: In October 2019, 48 mice were randomly divided into treated group and control groups: treated 4-week (P-4) group, treated 6-week (P-6) group, treated 8-week (P-8) group, control 4-week (C-4) group, control 6-week (C-6) group, and control 8-week (C-8) group. The treated group was injected with 15 mg/kg PQ solution and the control group was injected with 0.9% saline (0.2 ml/20 g) by intraperitoneal injection twice a week. After the initial state (0 weeks) and the treatment at the end of 4, 6 and 8 weeks, the mood changes and motor functions of mice were assessed by neurobehavioral tests (open field test, pole climbing test, tail suspension test and elevated plus maze test) . And the number of fecal pellets for 1 h and water content were calculated to assess the functional status of the gastrointestinal tract. Western blotting experiments were performed to detect the expression levels of α-synuclein (α-syn) and tyrosine hydroxylase (TH) in the nigrostriatal region of the mouse brain, the tight junction markers zonula occludens-1 (ZO-1) and Occludin, the inflammatory markers of integrin αM subunit (CD11b) , inducible nitric oxide synthase (iNOS) , high mobility group box 1 (HMGB1) , interleukin-1β (IL-1β) , and the neuronal markers βⅢ-tubulin and α-syn protein in the colon.Immunohistochemical staining was performed to detect the expression levels of colonic tight junction proteins ZO-1 and Occludin. Immunofluorescence staining was performed to detect the expression levels of TH in the substantia nigra region of the midbrain, and the co-localization of colonic intestine neuronal marker (βⅢ-tubulin) and Ser129 α-syn in the colonic. Results: Compared with the initial state (0 weeks) and C-8 group, mice in the P-8 group had significantly higher pole climbing test scores and resting time, and significantly lower total active distance, mean active speed, percentage of open arm entry and 1 h fecal instances (P<0.05) . After poisoning, the 1 h fecal water content of model mice first increased and then decreased, the P-4 and P-6 groups were significantly higher than the simultaneous point control group, and the P-8 groups were significantly lower than the initial state (P<0.05) . Compared with control, P-4 and P-6 groups, the expression levels of ZO-1 and Occludin in the P-8 group were significantly decreased (P<0.05) . Compared with control group, the expression levels of CD11b and IL-1β in the P-4 group were significantly increased (P<0.05) . Compared with control and P-4 group, the expression levels of CD11b, iNOS, HMGB1 and IL-1β in the P-6 and P-8 groups were significantly increased (P<0.05) . Compared with the control and P-4 groups, the expression levels of βⅢ-tubulin in the colon of mice in the P-8 group were significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased (P<0.05) . The expression level of Ser129 α-syn in the colon of model mice was negatively correlated with the expression level of βⅢ-tubulin (r(s)=-0.9149, 95%CI: -0.9771--0.7085, P<0.001) . Ser129 α-syn and βⅢ-tubulin co-localization in the colonic intermuscular plexus region increased gradually with the time of exposure. Compared with the control, P-4 and P-6 groups, the expression level of TH in the nigrostriatal region of the brain was significantly decreased, and the expression levels of α-syn and Ser129 α-syn were significantly increased in the P-8 group (P<0.05) . Correlation analysis showed that the relative expression level of Ser129 α-syn in the nigrostriatal region of the brain was negatively correlated with the expression level of TH in the model mice (r(s)=-0.9716, 95% CI: -0.9925--0.8953, P<0.001) . Conclusion: The PD mouse model is successfully established by PQ, and the intestinal function of the model mice is reduced in a time-dependent manner. And on this basis, it is preliminary determined that the abnormal aggregation of α-syn may be an important substance connecting the brain-gut axis.

Adolescent nicotine treatment causes robust locomotor sensitization during adolescence but impedes the spontaneous acquisition of nicotine intake in adult female Wistar rats

Very few people are able to quit smoking, and therefore it is essential to know which factors contribute to the development of compulsive nicotine use. These studies aimed to investigate if early-adolescent nicotine exposure causes locomotor sensitization and affects anxiety-like behavior and the spontaneous acquisition of intravenous nicotine self-administration. Early-adolescent male and female rats were treated with nicotine from postnatal (P) days 24 to 42, and anxiety-like behavior and locomotor activity were investigated one day after the cessation of nicotine treatment and in adulthood (>P75). The spontaneous acquisition of nicotine self-administration was also investigated in adulthood. The rats self-administered 0.03 mg/kg/infusion of nicotine for six days under a fixed-ratio (FR) 1 schedule and four days under an FR2 schedule (3-h sessions). Repeated nicotine administration increased locomotor activity, rearing, and stereotypies in a small open field in adolescent male and female rats. One day after the last nicotine injection, the percentage of open arm entries in the elevated plus-maze test was decreased in the males and increased in the females. However, locomotor activity in the small open field was unaffected. Adolescent nicotine treatment did not affect anxiety-like behavior and locomotor activity in adulthood. During the 10-day nicotine self-administration period, the females had a higher level of nicotine intake than the males. Adolescent nicotine treatment decreased nicotine intake in the females. In conclusion, these findings indicate that repeated nicotine administration during adolescence causes robust behavioral sensitization and leads to lower nicotine intake in females throughout the acquisition period in adulthood in rats.

Synthesis and Molecular Docking of novel 1,3-Thiazole Derived 1,2,3-Triazoles and In vivo Biological Evaluation for their Anti anxiety and Anti inflammatory Activity

Heterocyclic rings such as thiazole and triazole are considered as privileged moieties, since they constitute several drugs for biological treatment. In this work, a novel series of 1, 3-thiazole linked 1,2,3-triazole derivatives were designed and synthesized according to convenient synthetic procedures. All the synthesized compounds are characterized by 1H NMR, 13C NMR and LCMS techniques. The molecular docking was studied to illustrate the binding interactions of target molecules with GABAA receptor. The synthesized compounds containing 1,3-thiazole and 1,2,3-triazole ring, the presence of these rings in each molecule may lead to have potential in vivo anti-anxiety and anti-inflammatory properties. The in vivo activity result revealed that some of the compounds possessed statistical significant therapeutic efficacy. Anti-anxiety screening on mice indicated that all the target compounds (5mg/kg) exhibited certain extent of an anxiolytic effect by increasing time spent on open arms and the percentage of open arm entries as compared to controlled group. More importantly, among the newly synthesized compounds (6h) and (6i) have strong anti-anxiety against mice. The non steroidal anti-inflammatory activity drugs (NSAIDs) are plays a very important role to prevent the growth of cyclooxygenase enzymes which are responsible for inflammation and pain. The results show that the following compounds 6e, 6g, 6h, and 6k are having maximum anti inflammatory activity against carrageenan induced acute inflammation in rats comparable to diclofenac as reference drug. Molecular docking simulations were employed to find out the important binding modes responsible for the anti anxiety activity, thus supporting their effective anti-anxiety efficacy.

Involvement of the ventral, but not dorsal, hippocampus in anxiety-like behaviors in mice exposed to the elevated plus maze: participation of CRF1 receptor and PKA pathway.

The hippocampus is a limbic structure involved in anxiety-like behaviors. We aimed to evaluate the role of the dorsal (DH) and ventral (VH) hippocampus in anxiety-like behaviors in the elevated plus maze (EPM). We inhibited these brain regions using cobalt chloride (CoCl2: 1.0nmol) microinjections. We also investigated the involvement of corticotropin-releasing factor (CRF) action and protein kinase A (PKA) pathway using intra-DH and intra-VH microinjections of the CRF1 receptor antagonist CP376395 (0, 3.0, or 6.0nmol) and the PKA inhibitor H-89 (0, 2.5, or 5.0nmol). The results indicated that intra-VH CoCl2 microinjection increased the percentage of time spent and entries in the open arms. The mice also exhibited fewer stretch attend postures in the protected area and increased percentage of open arm entries. Further, intra-VH injection of 3.0nmol CP376395 increased time spent in the open arms. Intra-DH injection of 6.0nmol CP376395 increased the frequency of unprotected head dipping, whereas intra-VH injection of 6nmol CP376395 increased the frequency of protected head dipping. Intra-VH, but not intra-DH, microinjection of 2.5nmol H-89 increased the percentages of open arm entries and time spent in the open arms. Microinjection of 2.5 and 5.0nmol H-89 reduced the frequency of protected head dipping behavior. This study demonstrated that VH modulates anxiety-like behaviors in EPM. Moreover, CRF and the cAMP/PKA pathway seem to modulate these effects.

High-protein and low-calorie diets improved the anti-aging Klotho protein in the rats\u2019 brain: the toxic role of high-fat diet

BackgroundIn the current study, our specific aim was to characterize the Klotho protein and expression levels in the hippocampus and prefrontal cortex of old rats treated with different diets (high-fat, high-protein, low-calorie, high-protein and low-calorie).MethodsRats were treated with high-fat, high-protein, low-calorie, low-calorie high-protein diets for 10 weeks and then behavioral and molecular assessments were evaluated.ResultsStatistical analysis showed the percentage of open arm time was increased in the high-protein, low-calorie and low-calorie high-protein groups compared with old control (old-C) rats. The percentage of open arm entries was increased in the low-calorie and low-calorie high-protein group compared with old-C rats. The body weight and serum triglyceride were decreased in the low-calorie and low-calorie high-protein groups in comparison to control old rats. Low-calorie and low-calorie high-protein treatments statistically enhanced caspase-3 level compared with old-C rats in the hippocampus and prefrontal cortex. Treatment of old rats with high-protein, low-calorie and low-calorie high-protein could increase Klotho-α level compared with control old rats. The levels of Klotho-α, c-fos and brain-derived neurotrophic factors were decreased in the low-calorie high-protein group in Klotho inhibitor's presence compared with the low-calorie high-protein group.ConclusionAccording to our findings, Klotho-α level was reduced in old rats. Low-calorie, high-protein and particularly low-calorie high-protein diets increased this protein level and consequently increased neuronal plasticity and improved memory function.Graphic abstract

Bacopa monnieri alleviates aluminium chloride-induced anxiety by regulating plasma corticosterone level in Wistar rats.

Objectives Aluminium is present in food preparations, antacids and many medications. It causes neurodegeneration thereby resulting in a spectrum of neurological disorders such as dementia, Alzheimer's disease and anxiety. Bacopa monnieri (BM) is widely used in ayurvedic medicine to improve memory functions. Its anxiolytic property was investigated in this study by using elevated plus maze (EPM) and plasma corticosterone level. Methods Thirty rats were assigned into five groups. Control group received distilled water, and 0.5% tween 80, AlCl3 group received Aluminium Chloride (AlCl3), Protective groups (BM100+AlCl3 group and BM200+AlCl3 group) received AlCl3 and BM at two different doses, and the BM200 group received BM. The EPM experiment was performed at the end of the 4th week of oral administration of BM and AlCl3 followed by the measurement of plasma corticosterone. Results Oral administration of AlCl3 to rats increases the levels of anxiety as seen in a decrease in the percentage of entries into the open arms of EPM, an increase in grooming frequency and defecation index. However, the rats in the protective groups shown an increase in the percentage of open arm entries and rearing frequency, and decreased grooming frequency and defecation index. AlCl3 alone treated group showed a significant increase in the plasma corticosterone levels compared to the control group. Whereas the protective groups have shown a significant decrease in the plasma corticosterone levels than the AlCl3 alone treated group. Conclusions Hence the BM has potential role in reverting the anxiogenic effect of AlCl3 in the amygdala as it is evident from the plasma corticosterone levels and the EPM parameters of different groups under study.

Protective effect of fennel, and its major component trans-anethole against social isolation induced behavioral deficits in rats.

Social isolation damages the nervous system by weakening the antioxidant system and leading to behavioral disorders. Fennel (Foeniculum vulgare Mill.) is an herbal plant that has antioxidant and neuroprotective properties. The objective of this study was to evaluate the effect of fennel methanol extract and its major component trans-anethole on spatial learning and memory, anxiety and depression in male rats exposed to social isolation stress.Rats were divided into six groups of Control (C), Fennel (F), trans-Anethole (A), Isolation, Isolation-F and Isolation-A. The rats were kept in the cage alone for 30 days to induce isolation. Fennel extract (150 mg/kg) and trans-anethole (80 mg/kg) were also gavaged during this period. At the end of the course, spatial learning and memory, anxiety and depression were measured by Morris water maze (MWM), elevated plus maze (EPM) and forced swimming test (FST), respectively.Learning and memory were impaired in isolated rats. Swimming time and distance to reach the hidden platform in these animals increased compared with controls (P < 0.05). In the EPM test, the percentage of open arm entries and open arm time also decreased significantly in the Isolation group (P < 0.01). The immobilization time in FST also increased significantly in these animals compared with the Control group (P < 0.001). Fennel and trans-anethole were both able to eliminate these changes in isolated rats.It is concluded that fennel and its major component, trans-anethole are suitable candidates for the prevention and treatment of stress-induced neurological disorders.

5-HT1A and α2 adrenergic receptor levels are associated with high anxiety-like patterns and impulsivity in selectively bred Long Evans rats

Impulsivity and anxiety are psychological traits involved in many aspects of the drug addiction cycle. However, few preclinical models exist for examining both impulsive and anxiety patterns. In the current study, we investigated whether 6th generation rats selectively bred for high anxiety (HAn)-like behavior would display amphetamine (AMPH) hyperactivity. In the same generational line, we also determined if HAn animals would display impulsivity in an operant task. Filial 5 male Long Evans rats phenotyped as HAn and low anxiety (LAn) were tested on the elevated plus maze (EPM) and in locomotor chambers following a low dose of AMPH (0.5 mg/kg, IP). Next, a separate group of F5 animals was exposed to a differential reinforcement of low rate of responding (DRL: 30 s) operant schedule to assess impulsivity. Postmortem, 5-HT1A and α2 adrenergic receptor protein levels were measured in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) core and shell, and α2 adrenergic counts were assessed in the locus coeruleus (LC), and the paraventricular nucleus (PVN) of the hypothalamus. F5 outbred HAn rats had decreased percent open arm time and entries on the EPM and elevated AMPH-induced locomotion. In the DRL, HAn rats displayed an impulsive profile, they attained fewer total rewards, had more inter-response times, and showed greater burst ratios. We found that HAn rats had a higher number of 5-HT1A receptor immunostained cells in the mPFC but were not different than LAn in NAc core or shell. By contrast, levels of the α2 adrenergic receptor protein were no different in the mPFC while HAn rats had greater levels in the LC and lower levels in the PVN. Overall, these data further validate our outbred trait anxiety rats: HAn males show anxiety-like behavior, AMPH hypersensitivity, greater impulsivity, and varying levels of limbic and midbrain 5-HT1A and α2 adrenergic receptor proteins.

Combined use of alcohol and cigarette increases locomotion and glutamate levels in the cerebrospinal fluid without changes on GABAA or NMDA receptor subunit mRNA expression in the hippocampus of rats

Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.

Evaluation of anxiolytic properties of BacoMind extract of plant Bacopa monnieri Linn. in comparison with diazepam in rodent model

Background: Anxiety is a state characterized by somatic, emotional, cognitive, and behavioral components, associated with significant disability. The pharmacotherapy for anxiety remains limited for achievable safety and tolerability of the medicines. Benzodiazepines use associated with side effects like psychomotor impairment and addiction liability. Due to the ADRs associated with antianxiety drugs, the drug trials have focused on screening herbal medicines that are reportedly used in the treatment of anxiety and which have minimal side effects.Methods: The anxiolytic activity was examined by using the elevated plus maze (EPM) and open field test (OFT), forty Albino wistar strain rats of both sex of weighing 120 to 200 g were divided into four groups of ten rats each.. Group 1 received vehicle (normal saline); group 2 received diazepam (1 mg/kg); groups 3 and 4 received BacoMind™, 30 and 60 mg/kg oral, respectively.Results: Rats treated with diazepam (1 mg/kg, p.o.) showed significant (p&lt;0.001) increase in the percentage of open arms entries and time spent whereas, in closed arm the number of entries and time spent were significantly (p&lt;0.05) decreased. Intraperitonial administration of BacoMind™ extract of plant Bacopa monnieri Linn. exhibited significant (p&lt;0.05) increase in the number of open arm entries and time spent with significant (p&lt;0.05) reduction in number of entries and time spent in the closed arm as compared to group 1. BacoMind™ treated rats also produced significant increase in the number of rearings (p&lt;0.05), assisted rearings and number of squares crossed (p&lt;0.01).Conclusions: BacoMind™ extract of plant Bacopa monnieri Linn possess significant anxiolytic activity in the rats. It can be a promising anxiolytic agent.