The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval, and combining them attenuates the acquisition rate of spatial reference memory.

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over-generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.

Effects of antidepressants and soybean association in depressive menopausal women.

Depression in menopausal women has been widely described for many years ago and is related to hormonal decrease, mainly estrogens. The use of soy has been proposed as a possible coadjutant alternative to treat menopausal depressive disorder. In the present pilot clinical trial the effect of soybean, antidepressants and the association of soybean with antidepressants was studied in 40 depressive menopausal women for three months. Patients were divided in four groups of 10 women: fluoxetine (10 mg), soybean (100 mg), sertraline (50 mg), and sertraline (50 mg) plus soybean (100 mg). The Hamilton and Zung Depression Scales were used to measure the treatment effects. Values at the beginning and at the end of the study were compared. In all cases a significant difference was observed when the treated groups were compared vs. their untreated situation in both scales (p < 0.001). When a comparison between pre- minus post-treatment Zung scale scores was done, the effect induced by the association of sertraline and soybean was significantly higher than the other groups (p < 0.05). These effects were also seen using the Hamilton scale scores, showing significant differences between the association vs. soybean (p < 0.05) and setraline (p < 0.05) groups, but not vs. fluoxetine group. We conclude that soybean has an antidepressant effect per se, and the association of soybean and antidepressants increases their effects.

[Psychological Impact of COVID-19 on Health Workers During the Second Year of the Pandemic in Latin America: Cross-Sectional Survey Study]. / Impacto psicológico del COVID-19 en los trabajadores sanitarios durante el segundo año de pandemia en Latinoamérica: estudio de encuesta transversal.

Introduction: The coronavirus pandemic continues to affect the mental health of healthcare personnel in Latin America (LA). Objective: To estimate the prevalence of psychological disturbances and associated risk factors for mental health in healthcare personnel in LA during the second year of the COVID-19 pandemic. Method: This multicenter cross-sectional study included a total sample of 5437 healthcare professionals from Argentina, Bolivia, Chile, Colombia, Ecuador, and Peru. The PHQ-9, GAD-7, and a brief demographic questionnaire were used. The prevalence of anxiety and depression was estimated based on the cut-off points of the instruments. Two multivariate logistic regressions were performed. Results: A population burden of anxiety (40.1%) and depression (62.2%) was found in healthcare personnel in LA. Among professionals in Argentina (OR = 1.374; P<.001), those working in state hospitals (OR = 1.536; P<.003), frontline healthcare workers for COVID patients (OR = 1.848; P<.001), general practitioners (OR = 1.335; P<.001), and specialists (OR = 1.298; P<.001), a higher risk of experiencing mental disorders was observed. Among women, younger personnel, and administrative staff, a higher probability of experiencing anxiety and depression was identified. Conclusions: The burden of mental disorders on healthcare personnel in Latin America is alarming. Psychological support services are necessary, aimed at providing measures for professionals to develop healthy coping mechanisms that mitigate the impact of the pandemic on their well-being and facilitate post-crisis adjustment.

Acute Thalamic Ischemic Stroke in an Older Patient Newly Vaccinated with COVID-19 Vaccine Based on Adenoviral Vectors.

Introduction: Recent reports have shown several cases of cerebrovascular events after vaccination against COVID-19. The effects have been described mainly in women within the first two weeks of receiving the vaccine. Clinical Case: We describe here the first Colombian case of a cerebrovascular event after vaccination against COVID-19 in a 67-year-old woman with a vascular history. Four days after application of the messenger ribonucleic acid (mRNA) vaccine, she exhibited deviation of the labial commissure, ipsilateral ptosis, and limitation of march with lateralization. The event was associated with a subacute ischemic event in the right thalamus in parasagittal situation, changes in chronic ischemic microangiopathy of small vessels, and vascular crossing in the right cerebellar angle, without other alternative causes. Conclusion: The development and rapid use of vaccines has allowed the hospitalization and mortality statistics associated with COVID-19 to be reduced, but at the same time, it has generated concern about the potential side effects, generating controversy among the general population, especially in individuals with cardiovascular diseases. In our case, we provided evidence for the discussion of potential cerebrovascular events related to the application of vaccines in older people with a history of cerebrovascular diseases. This was done in order to analyze and control in subsequent studies the modulation of medical history on the likely effects of vaccination. However, despite the unavoidable side effects, the benefits of vaccination are superior.

[Prevalence and factors associated with subjective cognitive complaints in Latin American health workers during the COVID-19 pandemic]. / Prevalencia y factores asociados con las quejas cognitivas subjetivas del personal sanitario latinoamericano durante la pandemia de COVID-19.

Background and objectives: An increase in emotional disturbances and complaints about cognitive performance has been observed in Latin American healthcare workers during the SARS-CoV-2 pandemic, which can affect attention capacity and increase the levels of stress and burnout of these professionals. The objective was to analyse subjective cognitive complaints (SCC) and associated factors in health personnel during the COVID-19 pandemic in five Latin American countries.Methods: Multicentre cross-sectional study, which included 3,738 professionals from Colombia, Chile, Argentina, Ecuador, Bolivia, and Peru. The Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Mini-Z to assess Burnout. For the SCC, an item on cognitive concerns in attention and memory was used.Results: The prevalence of cognitive complaints was 69.2%. The factors associated with a higher risk of SCC were the scores in the GAD-7, PHQ and Mini-Z, in addition to being part of the Ecuadorian health personnel.Conclusions: There is a high prevalence of SCC in health personnel, which is modulated by emotional states and stress.

Clinical Heterogeneity in ME/CFS. A Way to Understand Long-COVID19 Fatigue.

The aim of present paper is to identify clinical phenotypes in a cohort of patients affected of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ninety-one patients and 22 healthy controls were studied with the following questionnaires, in addition to medical history: visual analogical scale for fatigue and pain, DePaul questionnaire (post-exertional malaise, immune, neuroendocrine), Pittsburgh sleep quality index, COMPASS-31 (dysautonomia), Montreal cognitive assessment, Toulouse-Piéron test (attention), Hospital Anxiety and Depression test and Karnofsky scale. Co-morbidities and drugs-intake were also recorded. A hierarchical clustering with clinical results was performed. Final study group was made up of 84 patients, mean age 44.41 ± 9.37 years (66 female/18 male) and 22 controls, mean age 45 ± 13.15 years (14 female/8 male). Patients meet diagnostic criteria of Fukuda-1994 and Carruthers-2011. Clustering analysis identify five phenotypes. Two groups without fibromyalgia were differentiated by various levels of anxiety and depression (13 and 20 patients). The other three groups present fibromyalgia plus a patient without it, but with high scores in pain scale, they were segregated by prevalence of dysautonomia (17), neuroendocrine (15), and immunological affectation (19). Regarding gender, women showed higher scores than men in cognition, pain level and depressive syndrome. Mathematical tools are a suitable approach to objectify some elusive features in order to understand the syndrome. Clustering unveils phenotypes combining fibromyalgia with varying degrees of dysautonomia, neuroendocrine or immune features and absence of fibromyalgia with high or low levels of anxiety-depression. There is no a specific phenotype for women or men.

Effects of atenolol injected into the nucleus accumbens septi in rats in the elevated plus-maze test.

Background In previous studies, we have observed that glutamate antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the elevated plus maze (EPM) test in rats. In the present study, the effect of Atenolol, a specific Beta Adreno-receptor antagonist in the EPM was studied in male rats bilaterally cannulated NAS. Methods Rats were divided into five groups that received either 1 µL injections of saline or atenolol in different doses (0.75, 1 or 2 µg/1 µL, n=15-16) 15 min before testing. Results Time Spent in the Open Arm was modified by treatment (F=4.563, p=0.006, df 3). This was increased by the lowest dose of atenolol (p<0.05), by the medium doses (p<0.001) and also by the highest dose (p<0.01). Time per Entry was modified by treatment (F=4.54, p=0.06, df 3). This parameter was increased by the lowest dose of atenolol (p<0.01), but not for the medium and higher doses. Conclusions We conclude that Atenolol beta receptor blockade in the accumbens lead to an anxiolytic-like effect related to an increase in the time spent in the open arm and in the time per entry, showing specific behavioral patterns.

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice.

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals - regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended.

Effects of dizocilpine-induced glutamatergic blockade in the nucleus accumbens septi on the plus maze test.

BACKGROUND: In previous studies, we have observed that specific N-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS. METHODS: Rats were divided into five groups that received either 1 µL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 µg, p<0.05), extreme arrivals were increased by the three higher doses (1 µg, p<0.05; 2 and 4 µg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 µg, p<0.05). A dose-effect relationship was observed in all cases. CONCLUSIONS: We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.

Behavioural consequences of nucleus accumbens dopaminergic stimulation and glutamatergic blocking in pigeons.

Upon systemic administration of apomorphine, a potent dopamine agonist, pigeons show a bout of pecking behaviour. When the drug is repeatedly administered a sensitization takes place that is associated with pronounced discrimination learning. Here we show that intra-cerebral injections of apomorphine in the periphery of the nucleus accumbens of pigeons also elicit pecking. We additionally show that injections of 5-amino-phosphonohepatnoic acid, a NMDA-glutamate receptor blocker, into the Acc impairs the performance of a learned visual discrimination incorporating pecking as a choice response. We conclude that, as it is the case in mammals, the control mechanisms of learned sensory-motor behaviour in birds involves dopaminergic and glutamatergic synaptic transmission within the nucleus accumbens area.

AP-7 into the nucleus accumbens disrupts acquisition but does not affect consolidation in a passive avoidance task.

The effect of the blockade of N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptors in the nucleus accumbens septi (Acc) during different phases of a passive avoidance task (step-through paradigm, two chambers) of learning was studied in male rats which had been bilaterally cannulated into the Acc. Animals were trained with a punishment procedure (3 s shock of 1 mA) to avoid one of the chambers. The rats received either saline or (+/-)2-amino-7-phosphonoheptanoic acid (AP-7) solution (1 microg/1 microl) 10 min before training (pretraining schedule) or immediately after the shock (posttraining schedule). In the test phase, the animals were placed back into the white chamber after 1 and 8 days later. In this moment, rats stayed there for 1 min, after which the time elapsed between the removal of the door to the introduction into the dark chamber of the head (Latency 1) and body (Latency 2) and fecal boli expelled were recorded. In the pretraining injection schedule, the drug treatment significantly reduced Latency 2 (P<.05) and fecal boli (P<0.01) on Day 1, and all parameters on Day 8 (P<.05). The posttraining injection schedule did not modify behavior. We conclude that a preshock NMDA-glutamatergic blockade of the Acc leads to cognitive disturbances during acquisition and a decrease in anxiety levels, but that the consolidation of a learned task is not affected by postshock administration.

Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test.

Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 microl injections of saline, (+/-)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 microg) or 2,3 dioxo-6-nitro-1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5, or 1 microg) 15 min before testing. Time spent in open arm, time per entry, end arrivals, open, closed, and total arm entries, relationship between open-, closed-, and total arm entries, rearing, face-, head-, and body grooming, and number of fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5 and 1 microg; P<.01) and NBQX (1 microg; P<.05) treatment, whereas time per entry was increased only with AP-7 (1 microg; P<.05). Open arm entries were increased by the intermediate doses of AP-7 (0.5 microg; P<.01) and NBQX (0.5 microg; P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5 microg/1 microl, P<.05). The frequency of rearing, grooming, and closed arm entries was not affected by the treatment. We conclude that NMDA and non-NMDA-glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical influences with the median doses, but that at higher doses the blockers have an anxiolytic-like effect.

Fear-potentiated behaviour is modulated by central amygdala angiotensin II AT1 receptors stimulation.

Central nucleus of the amygdala (CeA) is one of the most important regulatory centres for the emotional processes. Among the different neurotransmitter systems present in this nucleus, AT1 receptors have been also found, but their role in the generation and modulation of emotions is not fully understood. The present work evaluated the effect of intra-amygdalar injection of losartan (AT1 receptor antagonist) and angiotensin II (Ang II) in the anxiety state induced by fear-potentiated plus maze in male Wistar rats. Fear in the elevated plus maze can be potentiated by prior inescapable footshock stress. The decrease in the time spent in the open arms induced by the inescapable footshock was totally prevented by losartan (4 pmol) administration in CeA. It was also found that Ang II (48 fmol) administration decreased the time spent in the open arms in animals with or without previous footshock exposure. The locomotor activity and grooming behaviour were also evaluated. The results obtained from the different parameters analyzed allowed us to conclude that the Ang II AT1 receptors in CeA are involved in the anxiety state induced by stress in the fear-potentiated plus-maze behaviour.

Prepulse inhibition predicts working memory performance whilst startle habituation predicts spatial reference memory retention in C57BL/6 mice.

Prepulse inhibition (PPI) of the acoustic startle reflex refers to the attenuation of the startle response to an intense pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus. It is a well-established high-throughput translational measure of pre-attentive sensory gating, and its impairment is detected in several neuropsychiatric diseases including schizophrenia. It has been hypothesized that PPI might be associated with, or predictive of, cognitive deficiency in such diseases, and therefore provide an efficient assay for screening drugs with potential pro-cognitive efficacy. Free from any predetermined disease model, the present study evaluated in a homogeneous cohort of inbred C57BL/6 mice the presence of a statistical link between PPI expression and cognitive performance. Performance indices in a spatial reference memory test and a working memory test conducted in the Morris water maze, and contextual fear conditioning were correlated against pre-existing baseline PPI expression. A specific correlative link between working memory and PPI induced by weak (but not strong) prepulse was revealed. In addition, a correlation between habituation of the startle reflex and reference memory was identified for the first time: a stronger overt habituation effect was associated with superior spatial search accuracy. The PPI paradigm thus provides two independent predictors of dissociable cognitive traits in normal C57BL/6 mice; and they might serve as potential markers for high-throughput evaluation of potential cognitive enhancers, especially in the context of schizophrenia where deficits in startle habituation and PPI co-exist.

Baseline prepulse inhibition expression predicts the propensity of developing sensitization to the motor stimulant effects of amphetamine in C57BL/6 mice.

RATIONALE: The startle reflex to a sudden intense acoustic pulse stimulus is attenuated if the pulse is shortly preceded by a weak prepulse stimulus. This represents a form of sensory gating, known as prepulse inhibition (PPI), observable across species. PPI is modulated by dopamine and readily disrupted by acute amphetamine. Prior repeated exposures to amphetamine also disrupt PPI even when the drug is not present during test, suggesting that a sensitized mesolimbic dopamine system-inducible even by a single exposure to amphetamine-might be responsible. However, this causative link has been challenged by inconsistent efficacy between different amphetamine pre-treatment regimes, which all robustly sensitize the behavioral response to amphetamine. METHODS: Here, the presence of such a link in reverse was tested by comparing the propensity to develop amphetamine sensitization between high- and low-PPI expressing individuals identified within a homogeneous cohort of C57BL/6 mice. Comparison of dopamine content including its metabolites was performed separately in drug naïve mice by post-mortem HPLC. RESULTS: Behavioral sensitization was substantially stronger in the low-PPI group compared with the high-PPI group, while the magnitude of their response to the first amphetamine challenge was similar. Dopamine content within the nucleus accumbens and medial prefrontal cortex was significantly higher in low-PPI relative to high-PPI mice. CONCLUSION: Individuals with weak sensory gating characterized by low basal PPI expression may be more susceptible to the development of dopamine sensitization and therefore at greater risk of developing schizophrenia. Conversely, high baseline expression might predict a resistance to dopaminergic sensitization.

Differential behavioral profile induced by the injection of dipotassium chlorazepate within brain areas that project to the nucleus accumbens septi.

BACKGROUND: The effect of the agonism on γ-aminobutyric acid (GABA) receptors was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These structures send glutamatergic projections to the nucleus accumbens septi (NAS), in which interaction and integration between these afferent pathways has been described. In a previous study of our group, blockade of glutamatergic transmission within NAS induced an anxiolytic like effect. METHODS: Three rat groups received either saline or dipotassium chlorazepate (1 or 2 µg/1 µl solution) 15 min before testing. Time spent in the open arms (TSOA), time per entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and relationship between open- and closed-arms quotient (OCAQ) were recorded. RESULTS: In the AMY injected group TSOA, OAE and EA were increased by the higher doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA, OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p < 0.01) and saline injection showed an increasing significant difference (p < 0.001 in all cases) with the action of guide cannula alone within VH in TSOA, OAE and EA. CONCLUSION: We conclude that the injection of dipotassium chlorazepate has a differential effect depending of the brain area, leading to facilitatory and inhibitory effects on anxiety processing.

Intact working memory in the absence of forebrain neuronal glycine transporter 1.

Glycine transporter 1 (GlyT1) is a potential pharmacological target to ameliorate memory deficits attributable to N-methyl-d-aspartate receptor (NMDAR) hypofunction. Disruption of glycine-reuptake near excitatory synapses is expected to enhance NMDAR function by increasing glycine-B site occupancy. Genetic models with conditional GlyT1 deletion restricted to forebrain neurons have yielded several promising promnesic effects, yet its impact on working memory function remains essentially unanswered because the previous attempt had yielded un-interpretable outcomes. The present study clarified this important outstanding lacuna using a within-subject multi-test approach. Here, a consistent lack of effects was convincingly demonstrated across three working memory tests - the radial arm maze, the cheeseboard maze, and the water maze. These null outcomes contrasted with the phenotype of enhanced working memory performance seen in mutant mice with GlyT1 deletion extended to cortical/hippocampal glial cells. It follows that glial-based GlyT1 might be more closely linked to the modulation of working memory function, and raises the possibility that neuronal and glial GlyT1 may regulate cognitive functions via dissociable mechanisms.

Anxiolytic-like effect of losartan injected into amygdala of the acutely stressed rats.

It has been recognized that the stress-related peptides are involved in anxiety states. Angiotensin II receptor blockade by systemic administration of the AT(1) receptor antagonists has been proposed as a new treatment possibility for anxiety disorders. For better understanding of the related mechanisms, in this study we evaluated effects of bilateral intraamygdaloid injections of 2 (LOS 2) and 4 (LOS 4) µg of losartan (LOS), a selective AT(1) receptor antagonist, on the behavior of the not stressed and acutely stressed rats in an elevated "plus" maze. Under non-stress conditions, LOS 4 increased time spent in the open arms (p < 0.01), number of extreme open arm arrivals (p < 0.05), time per entry (p < 0.01), and the number of total arm entries (p < 0.05) showing thus considerable anxiolytic activity. The open arm extreme arrivals were increased by LOS 4 in both not stressed (p < 0.05) and stressed (p < 0.05) rats. When no stressed and stressed LOS 4 animals were compared, time per entry and the number of closed arm entries (p < 0.05, both) were decreased in the latter group. Moreover, the LOS 4 stressed rats had significantly increased open/closed arm quotient (p < 0.05) as compared to the both control and LOS 4 non-stress group (p < 0.05, both). These findings suggest that the AT(1) receptor blockade in amygdala is important for the anxiolytic action of LOS (and probably other AT(1) receptor blockers) under both non-stress and stress conditions.

Intra-amygdaloid microinjection of neuropeptide glutamic acid-isoleucine induces anxiety-like behavior.

The amygdaloid complex is involved in anxiety or fear responses to stressful stimuli. In this study the effect of neuropeptide-EI on anxiety-like behavior and its influence on adrenocortical function was tested in male Wistar rats that were injected bilaterally in the basolateral amygdala with neuropeptide-EI (1 µg/1 µl) or artificial cerebrospinal fluid and placed on the plus maze. The plasma corticosterone levels were analyzed in controls and plus-maze exposed animals. Neuropeptide-EI in the basolateral amygdala significantly decreased the time spent in open arms but had no effect on locomotor activity, showing an anxiogenic effect. However, neuropeptide administration did not change serum corticosterone levels compared with vehicle controls. Our results suggest that the anxiogenic effect of neuropeptide-EI could be independent of the hypothalamic-pituitary-adrenocortical system response.