Arm Entries Research Articles

The microinjection of a cannabinoid agonist into the accumbens shell induces anxiogenesis in the elevated plus-maze

This study investigated the effect of a cannabinoid agonist injected into the shell region of the nucleus accumbens (nAcb shell) on anxiety-related behaviors. The animals (male Wistar rats) were unilaterally microinjected with either ACEA (arachidonyl-2′-chloroethylamide a CB1 receptor agonist) at doses of 0.005, 0.05 or 0.5pmol, or vehicle (ethanol 0.04% in saline 0.9%) and submitted to the elevated plus-maze (EPM), a pre-clinical test of anxiety. The data showed that rats microinjected with ACEA (0.05pmol/0.2μl) into the nAcb shell exhibited decreased % open arm time and open arm entries in comparison with the control group, which is compatible with an anxiogenic-like effect. To rule out the hypothesis that spread of the drug into the ventricle was responsible for the observed anxiogenic effect, 0.05pmol ACEA was injected into the lateral ventricle and shown not to alter the responses representative of fear/anxiety and locomotion. The locomotor activity was not changed at the dose of 0.05pmol ACEA microinjected into the nAcb shell. The present data suggest that activation of cannabinoid receptors in the nAcb shell may modulate fear/anxiety in the EPM.

Effect of biphenyl dimethyl dicarboxylate and fluoxetine on performance of normally-fed and protein malnourished psychologically stressed mice in elevated plus maze

Stress alters psychological diseases such as anxiety and depression. Protein malnutrition (PM) contributes to psychological disorders. The present study aimed to investigate the effect of biphenyl dimethyl dicarboxylate (DDB) on anxiety of psychologically stressed protein malnourished mice as compared to its effect in normally-fed mice. Fluoxetine (FLX) was used as reference standard. Animals were randomly divided into two major groups, normally-fed group provided with 20% casein diet and a protein malnourished one was provided with a diet containing 8% casein for 21 consecutive days. The given diet was continued during the experiment. Stress was induced using the learned helplessness technique (LH). Each animal was exposed for 5days to the psychological stress session either alone or in association with drug administration following completion of 21days under the selected diet regimen. DDB and fluoxetine were given in doses of 100mg/kg p.o. and 10mg/kg i.p., respectively before exposure to foot shocks daily. Anxiety was evaluated using elevated plus maze (EPM) and the whole brain wet tissue monoamine levels, namely dopamine, norepinephrine and serotonin were estimated.Protein malnutrition in the presence of stress resulted in increasing number of open arm entries and head dipping as compared to the normally-fed stressed mice. Stress in the presence or absence of protein malnutrition significantly increased rearing frequency as compared to the corresponding mice. Fluoxetine in the presence of stress significantly decreased open arm time spent and number of open arm entries as compared to protein malnourished stressed mice. Protein malnutrition increased stretched attend posture.

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

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

The effect of quetiapine (Seroquel™) on conditioned place preference and elevated plus maze tests in rats when administered alone and in combination with (+)-amphetamine.

Recent case reports describe recreational use of quetiapine and drug-seeking behaviour to obtain quetiapine, an atypical antipsychotic. We examined the hypothesis that quetiapine (10, 20 or 40mg/kg) alone or co-administered with (+)-amphetamine (0.25, 0.5, 0.75 or 2.0mg/kg) will affect reward and/or decrease anxiety in rats, as measured by conditioned place preference (CPP) and elevated plus maze (EPM) test, respectively. Quetiapine (20mg/kg) produced greater open arm time and entries in the EPM test compared to 10 and 40mg/kg, and quetiapine (10mg/kg) significantly increased open arm entries and time when co-administered with (+)-amphetamine (0.5mg/kg) compared to (+)-amphetamine (0.5mg/kg) alone, suggesting decreased anxiety. Quetiapine (10, 20 or 40mg/kg) produced no CPP when administered alone; the lowest dose of quetiapine (10mg/kg) reduced CPP produced by a low dose of (+)-amphetamine (0.25mg/kg), but had no significant effect on CPP produced by a higher dose (0.5mg/kg). The quetiapine-induced anxiolytic effect in the EPM might explain why humans are misusing quetiapine and combining it with (+)-amphetamine. It is possible that humans experience an anxiolytic effect of the combined drugs and relatively unaltered rewarding effects of (+)-amphetamine. The results shed some light on the question of why humans are abusing and misusing quetiapine, despite its dopamine (DA) D2 receptor antagonism; it will be the task of future studies to identify the pharmacological mechanism mediating this behaviour.

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

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

Anti-stress effect of astragaloside IV in immobilized mice

Ethnopharmacological relevanceAstragaloside IV, a major component extracted from the roots of Astragalus membranaceus (AM), possesses anti-inflammatory, anti-oxidative, anti-fibrotic, anti-infarction and immunoregulatory effects. To clarify anti-stress effect of AM, anxiolytic and anti-inflammatory effects of 80% ethanol extract of AM and astragaloside IV were investigated in immobilization stress model. Materials and methodsThe mice were orally administered with AM (50, 200, and 500mg/kg), astragaloside IV (5, 10, and 20mg/kg) and buspirone, a positive drug, 1h before immobilization treated for 2h. For anxiolytic activity assay, EPM test was performed in mice. For anti-inflammatory activity assay, serum levels of corticosterone, IL-6 and TNF-α were measured using ELISA kits. ResultsAM extract and astragaloside IV increased dose-dependently time spent on open arms and open arm entries in the EPM test. Anxiolytic effects of AM extract (500mg/kg) and astragaloside IV (20mg/kg) were comparable to those of buspirone (1mg/kg). Their anxiolytic effects were blocked by WAY-100635 (0.5mg/kg, i.p.), a 5-HT1A receptor antagonist (p<0.01), but not by flumazenil (3mg/kg, i.p.) and bicuculline (0.5mg/kg, i.p.), GABAA receptor antagonists. AM extract and astragaloside IV also reduced serum levels of corticosterone, IL-6 and TNF-α dose-dependently. ConclusionsAM, particularly astragaloside IV, may ameliorate immobilized stress-induced anxiety and inflammation.

Emblica officinalis outcome on noise stress induced behavioural changes in Wistar albino rats

Exposure to any kind of noise exceeding 90 dB is reported to be a stressor. This study focuses on whether Emblica officinalis supplement (333 mg/kg/b.wt) could avert the noise stress induced behavioural changes in Wistar albino rats. Noise stress animals were exposed to 100 dB (4 hr/day) for 15 days. When compared to control and E. officinalis treated animals, noise stress animals showed an increased immobilization, rearing, fecal bolus and marked decrease in ambulation and grooming in open field test, whereas in elevated plus maze, it showed a marked decrease in the number of open arm entry and percentage, time spent in open arm and percentage. Noise stress animals treated with E. officinalis showed improvement in all the above observations and recovered from the stress. The results imply that E. officinalis possesses anti-stressor property by reducing the noise stress induced alterations in behaviour, its effect might be due to the antioxidant property of E. officinalis.

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

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

Chronic exercise improves repeated restraint stress-induced anxiety and depression through 5HT1A receptor and cAMP signaling in hippocampus.

[Purpose]Mood disorders such as anxiety and depression are prevalent psychiatric illness, but the role of 5HT1A in the anti-depressive effects of exercise has been rarely known yet. We investigated whether long-term exercise affected a depressive-like behavior and a hippocampal 5HT1A receptor-mediated cAMP/PKA/CREB signaling in depression mice model.[Methods]To induce depressive behaviors, mice were subjected to 14 consecutive days of restraint stress (2 hours/day). Depression-like behaviors were measured by forced swimming test (TST), and anxiety-like behavior was assessed by elevated plus maze (EPM). Treadmill exercise was performed with 19 m/min for 60 min/day, 5 days/week from weeks 0 to 8. Restraint stress was started at week 6 week and ended at week 8. To elucidate the role of 5HT1A in depression, the immunoreactivities of 5HT1A were detected in hippocampus using immunohistochemical technique.[Results]Chronic/repeated restraint stress induced behavioral anxiety and depression, such as reduced time and entries in open arms in EPM and enhanced immobility time in FST. These anxiety and depressive behaviors were ameliorated by chronic exercise. Also, these behavioral changes were concurrent with the deficit of 5HT1A and cAMP/PKA/CREB cascade in hippocampus, which was coped with chronic exercise.[Conclusion]These results suggest that chronic exercise may improve the disturbance of hippocampal 5HT1A-regulated cAMP/PKA/CREB signaling in a depressed brain, thereby exerting an antidepressive action.

Dorsal hippocampus histaminergic and septum GABAergic neurons work in anxiety related behavior: Comparison between GABAA and GABAB receptors

Background: Integration of septum and hippocampus has an important role in anxiety modulation and inhibition. Our previous studies indicated that GABAergic system blockade in the medial septum (MS) attenuates anxiety-like behavior. Herein, we aimed to investigate the histaminergic and GABAergic associations between dorsal hippocampus and MS, respectively. Moreover, the present study compares the power of two kinds GABA receptors, GABA A and GABA B receptors, in MS in anxiety related behavior of male rats. Methods: In the present study we investigated the intrahippocampal CA1 (intra-CA1) microinjection of histamine and intra-septal GABAergic agents on anxiety-related behavior in rats, using elevated plus-maze test of anxiety. Results: Intra-CA1 administration of histamine increased open arm time (%OAT) and open arm entry (%OAE). Intra-septal administration of the GABA A agonist muscimol (10 ng/rat) increased %OAE and %OAT but not locomotor activity. Administration of muscimol (2.5 and 5 ng/rat) had no effect on anxiety, while co-administration of sub-effective dose of histamine (1 µg/rat) into CA1 and sub-effective dose of muscimol (2.5ng/rat) into medial septum area increased %OAE and %OAT. Administration of GABA A receptor antagonist confirmed GABA A function in the medial septum. In contrast, injection of GABA B receptor agonist decreased OAT and OAE percentage. Microinjection of GABA B receptor antagonist revealed that this GABA receptor increased the anxiety in the rats by a different mechanism. Conclusion: The effect of histamine on anxiety in CA1 may be modulating through septal GABAergic system and GABA A receptor is involved in the process

NK1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats

Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1mg/kg) followed 30min later by saline or PILO (350mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100pmol) – an NK1 receptor antagonist – were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head-dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic-like profile induced by PILO in rats evaluated in the EPM test.

Effect of hypothyroxinemia on the emotion in developing rats

Objective To investigate the effect of hypothyroxinemia on emotion and hippocampus neurons in developing rats.Methods Sixty-nine healthy postnatal day (PD) 1 rats were randomly divided into control group (n =36) and experimental group (n =33).On PD1,experimental group was bilaterally thyroidectomized to establish hypothyroxinemia model,the control group was only given thyroid exposure operation without thyroid resection.On PD10,21,40,serum triiodothyronine (T3),thyroxine (T4),thyrotropicstimulating hormone (TSH) were detected by radioimmunoassay.Tail suspension test,forced swimming test,the elevated-plus maze and open field were respectively employed to detect the anxiety/depression like behavior on PD30,31,32,33.Nisslg staining was used to determine the survival of neurons at PD10,21,40 in hippocampus CA1,CA3,DG regions.Results Serum T4 levels on PD10,21,40 in experimental group decreased significantly as compared with control group (P ＜0.01),while there was no significant difference in serum T3 or TSH level (P ＞ 0.05).In the tail suspension test,immobility time of experimental group [(197.00 ± 19.50) s] was longer than control group [(158.33 ± 32.90) s,P ＜0.05].In the forced swimming test,immobility time of experimental group[(92.11 ± 35.24) s] was longer than control group [(62.00 ± 23.73) s,P ＜ 0.05].In the elevated plus-maze test,total number of arm entries and closed arm entries in experimental group were increased as compared with control group(P ＜ 0.05),percentage of closed arm/total time of experimental group was decreased as compared with control group(P ＜ 0.05).In the open field,there was no obvious difference between the two groups(P ＞ 0.05).On PD10,21,40,the amount of neurons in DG region of experimental group were less than control group(P ＜0.05),while there was no significant difference in CA1 or CA3 on PD10,21,40(P ＞0.05).Contusions Hypothyroxinemia can cause depression,hyperactivity and hippocampus neuron damage of developing rats. Key words: Hypothyroxinemia; Rat; Depression; Anxiety; Emotion; Hippocampus

An Intra-hippocampal Injection of Nandrolone Induces Learning and Memory Impairments in Rat

This study was investigated to evaluate the effect of intra-hippocampal injection of the nandrolone on spatial learning task in rats. The drug or vehicle was manually injected into the hippocampus with a 10-µl Hamilton syringe attached via polyethylene tubing to 27-gauge stainless-steel injection cannula. After 6 days of recovery, learning behaviors were evaluated using an 8-arm radial maze. The results showed that intra-hippocampal injection of nandrolone can impair trained spatial learning at a dose of 5 µl. We also observed a dense cytoplasm and nucleus in CA1 neurons as well as signs of necrosis. Nandrolone can impair the time required to reach the baited arm as well as the frequency of successful arm entries. At the 10 µl dose of nandrolone, neural hypertrophy and increased dentate gyrus volume were also observed.

Apigenin 7-glucoside from Stachys tibetica Vatke and its anxiolytic effect in rats

BackgroundStachys tibetica Vatke (Himalayan or mountain tea) grows abundantly in the tropical and subtropical locations of the world including India, Tibet and China. The traditional healers of Kargil and adjoining areas in Ladakh, Jammu and Kashmir in India use the drug to treat fever, cough, phobias and various mental disorders etc. in the form of a decoction or as a tea. Flavonoids are important components in most herbal teas and play an important role in the management of various brain disorders via mimicking the action of benzodiazepines or through benzodiazepine receptors. Aim of the studyThe present study aimed to isolate flavonoids from S. tibetica and to evaluate their anxiolytic potential in comparison to reference synthetic (diazepam) and natural (apigenin) molecules. Materials and methodsS. tibetica root powder was extracted with 95% methanol for about 72h using a soxhlet apparatus and the resultant extract was subjected to isolation procedures, resulting in the isolation of apigenin 7-glucoside and characterisation by various physical and spectrometric analyses. Apigenin 7-glucoside was evaluated for anxiolytic activity in rats in comparison with the reference compounds diazepam and apigenin using the elevated plus maze (EPM) model. ResultsPhytochemical investigations of S. tibetica revealed the presence of tannins, phenolics, flavonoids, saponins, glycosides and carbohydrates. A flavonoid glucoside, apigenin 7-glucoside was isolated for the first time from the roots of S. tibetica Vatke. The percentage of time spent and arm entries in the open arms was increased while the arms entries and duration of time spent in closed arms were decreased in the groups treated with apigenin 7-glucoside (which dose). In a similar fashion, diazepam and apigenin also exhibited anxiolytic activity (*p<0.05, **p<0.01). Apigenin 7-glucoside significantly decreased the percentage of head dips in EPM. Apigenin 7-glucoside showed anxiolytic potential comparable to the reference drugs apigenin and diazepam. ConclusionApigenin 7-glucoside could be an important molecule for the treatment of anxiety and further studies are required to elucidate its possible mechanism of action.

Dentin hypersensitivity induces anxiety and increases corticosterone serum levels in rats

AimsInvestigate the relationships between experimentally induced dentin hypersensitivity (DH) with behavioral, endocrine and dentin erosion data. MethodsMale Wistar rats divided into four groups, two controls and two experimental, received tap water or isotonic solution (Gatorade®, lemon, pH2.7) for 30 or 45days. The DH test was performed by a cold water stimulus on molars. A score (0–3) was given to the rats' pain response. Anxiety was evaluated by the elevated plus maze model and by serum corticosterone levels. The dentin erosion was observed by scanning electron microscopy (SEM). Anatomopathological studies were performed on the stomach, adrenal, kidney, and liver. ResultsRelative to control groups, experimental rats showed: 1) increased hypersensitivity scores (control group, 0; experimental groups, 2 (limits 0.5–3) on the 30th day and 2 (limits 1–3) on the 45th day); 2) reduced percentage of time and entries in the open arms and in serum corticosterone levels; 3) totally exposed dentinal tubules on the 30th day in SEM analysis of the teeth; and 4) no alterations in the anatomopathological and histological evaluations. ConclusionsThe treatment with isotonic solution for 30days was able to induce DH after erosive challenge and severe DH was observed after isotonic solution treatment for 45days. The pain induced by cold stimuli was consistent with the grade of DH. The close relationships between dental erosion, response to pain, serum levels of corticosterone and the EPM behavior responses reveal the effects of DH at several levels.

Cognitive Deficits and Disruption of Neurogenesis in a Mouse Model of Apolipoprotein E4 Domain Interaction

Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in apoE4 carriers. Accumulating data suggest that the interaction between the N- and the C-terminal domains in the protein may be the main pathologic feature of apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain interaction, by introducing the domain interaction feature of human apoE4 into native mouse apoE. We carried out hippocampus-dependent learning and memory tests and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age-matched background C57BL/6J mice. Learning and memory task performance were impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice. Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J mice. These early-age neurotrophic and neurogenic (proliferative) effects in the Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to "repair" itself. This is supported by the higher cleaved caspase-3 levels in the young animals that not only persisted, but increased in old age, and the lower levels of doublecortin at old age in the hippocampus of Arg-61 mice. These results are consistent with human apoE4-dependent cognitive and neuro-pathologic changes, supporting the principal role of domain interaction in the pathologic effect of apoE4. Domain interaction is, therefore, a viable therapeutic/prophylactic target for cognitive impairment and AD in apoE4 subjects.

Effect of resveratrol on behavioral performance of streptozotocin-induced diabetic mice in anxiety tests.

The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare.

Deuterium depletion induces anxiolytic-like effects in rats

Deuterium-depleted water (DDW) has a concentration of deuterium 6-7 times lower than naturally occurring water (20-25 ppm vs. 150 ppm). When administered for a longer period, it can reduce the concentration of deuterium throughout the body, activating cellular mechanisms that depend on protons. The aim of the present work was to investigate the influence of chronic DDW administration on anxiety-related processes in Wistar rats when compared to a control group that received distilled water, as studied in an elevated plus maze behavioral test. Our results describe a possible anxiolytic-like effect of DDW administration on rats, as shown by the increase in the percentage of time and number of entries in the open arms of the elevated plus maze. The administration of DDW also resulted in stimulated head-dipping behavior in the open arms, which is a behavioral change that characterizes the exploratory behavior and decreased inhibition/ fear in an unfamiliar environment. We conclude that the change in this balance may have important consequences for many biological mechanisms. A deuterium desaturation treatment with DDW might have a use in anxiety disorders.

Effects of Buspirone on Anxiolytic Effects of Magnesium in Male Mice

Anxiolytic-like activity of magnesium chloride has been exhibited in the elevated plus-maze test in mice, in several studies. Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class that is not related to benzodiazepines, unlike most drugs predominately used. The purpose of the present study was to examine interaction between magnesium (Mg) and buspirone as a partial agonist of 5-HT1A receptors in producing anxiolytic-like activity in the elevated plus maze. The anxiolytic-like effect of Mg (50, 100 and 200 mg/kg, orally), buspirone (5 mg/kg, i.p) and its interaction with Mg (50 mg/kg) was evaluated after ten days treatment. Mg given at all doses (50, 100 and 200 mg/kg) and buspirone (5 mg/kg) induced an anxiolytic-like effect significantly increasing the percentage of the time spent in the open arms (%OAT), the percentage of the open arm entries (%OAE) and number of total entries. Percent time spend in open arms was reduced when buspirone coadministered with Mg (50 mg/kg) compared to Mg alone. However, the number of entries did not change significantly. No synergistic interaction (increased time in open arms and number of open arm entries) between Mg and buspirone was observed, in this test, on the contrary, %OAT preserved about buspirone effects and %OAE remained around Mg effect. The obtained data indicate that Mg may act partly via serotonergic receptors due to buspirone’s inhibitory action as a partial agonist of serotonin receptor.

Effect of Chronic DL-Amphetamine Exposure on Brain Volume, Anxiogenic, Locomotor, and Social Behaviors in Male SD Rats

Research examining the long-term effects of drugs such as AdderallTM, a mixed DL-amphetamine, as a first-line treatment strategy for those diagnosed with attention deficit hyperactivity disorder (ADHD), is very much lacking. In order to address this, the present study sought to examine possible behavioral and neuroanatomical effects of chronic oral exposure to DL-amphetamine administered at a relatively low dose to the developing male Sprague Dawley rat. Animals were administered a mixture of chocolate drink and DL-amphetamine at a dose of 1.6 mg/kg for 36 days, beginning at PD 24 and ending at PD 60. Anxiety, a potential side effect of stimulant treatment, was assessed using three paradigms: The open field test (OF), the social interaction test (SI), and the elevated plus maze (EPM). The OF and SI were conducted using repeated testing over the course of five weeks. Testing occurred immediately after drug administration on a given day. The EPM was used only once on the penultimate day of treatment, before the drug was administered. Following drug treatment on PD 60, brain-to-body weight ratios were obtained. Results indicated that there were no group differences in brain-to-body weight ratios nor were differences in locomotor and social behaviors observed. However, rats treated with DL-amphetamine did show an anxiogenic response in the EPM. This was represented as a significant reduction in open arm entries. Overall our findings suggest that while chronic drug treatment fails to alter multiple measures of behavior, or reliable changes in brain volume, such treatment may impact a behavioral index of anxiety. Future research should seek to examine the implications of this heightened anxiogenic response in animals treated chronically with oral, low-dose DL-amphetamine.