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Objective: Communication between patients and mental health professionals by means of messaging platforms in the interval between synchronous encounters became a kind of asynchronous teleconsultation (AT) whose usefulness and effect on providers’ workload have not been explored. Method: Mental health providers working in Argentina were invited to answer a survey exploring the intensity and usefulness of AT, and the resulting overload., Results: A total of 527 responses from professionals working throughout the country were received. As much as 69% of respondents exchanged messages with a mean of 1-10 patients/day and 31% with more than 10 patients/day; 75% answered messages over mobile phones on weekends. While 68% rated these interactions as positive for clinical follow-up, 47% considered them as a source of work overload., Conclusions: The generalized adoption of AT may require additional self-regulation by clinicians and regular monitoring of overload levels (particularly, among psychiatrists) to make their daily clinical practice efficient and sustainable., (CC BY NC ND)

Background: Between 25% and 50% of patients suffering from treatment-resistant schizophrenia fail to achieve a clinical response with clozapine. The rapid identification and treatment of this subgroup of patients represents a challenge for healthcare practice., Aims: To evaluate the relationship between metabolic alterations and the clinical response to clozapine., Methods: A multicenter, observational, case-control study was performed. Patients diagnosed with schizophrenia treated with clozapine were eligible (minimum dose 400 mg/d for at least 8 weeks and/or clozapine plasma levels ⩾ 350 µg/mL). According to the Positive and Negative Syndrome Scale (PANSS) total score, patients were classified as clozapine-responsive (CR) (<80 points) or clozapine non-responsive (CNR) (⩾80 points). Groups were compared based on demographic and treatment-related characteristics, together with body mass index (BMI), waist circumference, insulin, leptin, and C-reactive protein plasma levels. Plasma levels of clozapine and its main metabolite, nor-clozapine, were measured in all the participants. In addition, the potential relationship between PANSS scores and leptin or insulin plasma levels was assessed., Results: A total of 46 patients were included: 25 CR and 21 CNR. BMI and waist circumference, fasting insulin and leptin plasma levels were lower in the CNR group, while C-reactive protein was not different. Moreover, significant negative correlations were observed between PANSS positive and general psychopathology subscores, on one hand, and insulin and leptin plasma levels, on the other hand, as well as between PANSS negative subscores and leptin plasma levels., Conclusions: Our results suggest that the lack of metabolic effect induced by clozapine is associated with the lack of clinical response., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The purpose of this study was to asess the efficacy of an intensive outpatient treatment (IOT) for substance use disorder (SUD) using a multidimensional approach., Methods: All the patients consecutively admitted to a private institution between May 2019 and May 2020 were invited to participate in the study. The program consisted in a 12-month set of psychosocial, medical and recreative interventions requiring an attendance of at least 9 hours per week. Efficacy was evaluated at admission and every three months by the Addiction Severity Index (ASI). Quality of life was evaluated at admission and at the end of the treatment by the WHOQOL-Bref questionnaire. A comparison of parameters obtained at admission between the group that completed and the one that abandonned the treatment was also performed to detect potential predictors of early dropout. Six months after the end of the treatment, the participants were contacted in order to repeat an evaluation through the ASI and the WHOQOL-Bref scales., Results: 41 participants (73% male, age 42.8 ± 16 years) were included. 14 participants dropped out at a median time of 88 days. Among those who completed the treatment improvements were observed in different clinical dimensions: in alcohol and drug consumption (3 months), in medical problems (6 months), in family/social relationships (9 months), in psychological scores (12 months) and in the four dimensions of WHOQOL-Bref. No changes were observed in legal problems and in the employment status. Only legal problems and family/social relationships at admission were significantly different among patients who completed versus those who dropped-out. Six months after discharge, no differences in WHOQOL-Bref scores were observed in the 15 participants who could be located and accepted the assessment. A little but statistically significant worsening was observed in the psychological problems dimension of the ASI in post-discharge follow-up. The rest of the ASI dimensions remained unchanged 6 months after concluding the treatment., Conclusion: This is one of the few studies performed in a latinamerican setting assessing the efficacy of a long-term IOT for SUD. It confirms previous works from developed countries, showing the potential benefits of IOTs implementation in our region., (CC BY NC ND)

The hen's egg test on chorioallantoic membrane (HET-CAM) is one of the most frequently used alternative tests for prediction of ocular irritation of cosmetic products. There are different HET-CAM protocols widely accepted, but there is no information about which of the protocols better correlates with the results obtained in product use clinical study under the conditions of use. Two Fix Time Methods (FTM) -Lüepke and the ICCVAM guideline - and two Reaction Time Methods (RTM) -ECVAM DBALM Prot. No. 47 and No. 96- were employed to test 18 cosmetic products. Simultaneously, they were evaluated by an ophthalmological clinical test. A unified classification system was used, and products were classified into four irritation levels: non-irritant, weak, moderate and severe irritant. The duration of use (rinse-off or leave-on), and the concentration and type of surfactants were taken into account in the analysis. All the products that were classified as non-irritant by any HET-CAM protocols were also safe in the product use clinical study. The product that was found to be non-safe in the product use clinical evaluation was also unsuitable by most of the HET-CAM protocols. These results were employed to develop an algorithm that allows selecting the appropriate HET-CAM protocol for each type of product to be tested., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In clinical practice it is increasingly imperative to obtain updated information for decision making. For health professionals, it is of great value to collect the experience that other workers in the disciplinary field have synthesized in the form of articles, reviews or different types of reports. Moreover, having tools that allow weighing the internal and external validity of the publications found, provides skills that today are essential for a clinical practice that guarantees patients the best standards of care. These notes are intended to guide readers in obtaining and assessing the information available for reasoned decision making.

Persons with mental disorders present higher morbimortality than that observed in general population. Among the factors contributing with this situation we can mention an increase in the incidence of obesity and metabolic syndrome, with their burden of cardiovascular and cancer risks. This review summarizes the evidence about the comorbid presence of schizophrenia, unipolar depression and bipolar disorder on one side and metabolic syndrome or obesity on the other. We also review the different causes of such comorbidity, in particular the adverse effects of psychotropic drugs, diverse biological factors predisposing to the increase in body weight and the measures that can be taken in order to attenuate or prevent metabolic disease in persons affected by mental illness.

Background: Scarce information is available about how users experience treatment at mental health day hospitals, particularly in South America., Aims: To explore users' perspectives about elements of day hospital treatment that facilitate or hinder the recovery process in a mental health facility in Buenos Aires, Argentina., Methods: Semi-structured individual interviews (n = 8) and focus groups (n = 4) were carried out with a convenience sample of users of a mental health day hospital program based on a formulation, testing and redevelopment of propositions approach. Results were analyzed through grounded theory techniques., Results: Categories indicating recovery were: starting to do things, being able to see themselves from a new perspective, mood improvement and changes in interpersonal relationships. Aspects facilitating recovery were: activities organized by the facility, the group approach, the care provided by facility workers and the physical environment. Hindering aspects were: heterogeneity of users in terms of age, severity, diagnosis and being underestimated by staff., Conclusions: Being active again was considered to be the main recovery indicator in this cultural context and participating in activities led by skilled facilitators was the most beneficial factor of the program according to the users.

Praziquantel (PZQ) is an anthelmintic drug used both in humans and animals that can be administered through various routes. There are transdermal formulations for cats, but only oral or subcutaneous dosage forms for dogs. Given the fact that the cat's skin and the dog's skin have different characteristics, which in turn affect bioavailability, we developed a PZQ spot-on formulation for dogs. This study was aimed at determining the plasmatic behavior of topically administered PZQ (Labyes ® ) in adult dogs. Dogs were administered PZQ (14.5mg/kg PZQ, from a solution of 100mg/ml). Blood samples were drawn before treatment onset and at the following time points after PZQ administration: 1, 2, 4, 6, 12, 24 and 48h. PZQ plasma concentration was determined by ultra-high performance liquid chromatography (UPLC) coupled to tandem mass spectrometry (MS/MS). Observed maximum concentration (C max ), area under the concentration-time curve from the time of drug administration to infinity (AUC inf ) and time to maximum concentration (T max ) were calculated for each animal, and mean±SD for each parameter was obtained. Results were as follows: C max =56.0±15ng/ml; AUC inf =910.2±220ng*h/ml, T max =5.0±1.1h. This is the first study to provide pharmacokinetic data of a praziquantel spot-on formulation for dogs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Working memory is a cognitive function serving goal-oriented behavior. In the last decade, working memory training has been shown to improve performance and its efficacy for the treatment of several neuropsychiatric disorders has begun to be examined. Neuroimaging studies have contributed to elucidate the brain areas involved but little is known about the underlying cellular events. A growing body of evidence has provided a link between working memory and relatively long-lasting epigenetic changes. However, the effects elicited by working memory training at the epigenetic level remain unknown. In this study we establish an animal model of working memory training and explore the changes in histone H3 acetylation (H3K9,14Ac) and histone H3 dimethylation on lysine 27 (H3K27Me2) triggered by the procedure in the brain regions of the corticostriatothalamic circuit (prelimbic/infralimbic cortex (PrL/IL), dorsomedial striatum (DMSt) and dorsomedial thalamus (DMTh)). Mice trained on a spontaneous alternation task showed improved alternation scores when tested with a retention interval that disrupts the performance of untrained animals. We then determined the involvement of the brain areas of the corticostriatothalamic circuit in working memory training by measuring the marker of neuronal activation c-fos. We observed increased c-fos levels in PrL/IL and DMSt in trained mice 90min after training. These animals also presented lower immunoreactivity for H3K9,14Ac in DMSt 24h but not 90min after the procedure. Increases in H3K27Me2, a repressive chromatin mark, were found in the DMSt and DMTh 24h after the task. Altogether, we present a mouse model to study the cellular underpinnings of working memory training and provide evidence indicating delayed chromatin remodeling towards repression triggered by the procedure., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rationale: Stress is a common antecedent reported by people suffering major depression. In these patients, extrahypothalamic brain areas, like the hippocampus and basolateral amygdala (BLA), have been found to be affected. The BLA synthesizes CRF, a mediator of the stress response, and projects to hippocampus. The main hippocampal target for this peptide is the CRF subtype 1 receptor (CRF1). Evidence points to a relationship between dysregulation of CRF/CRF1 extrahypothalamic signaling and depression., Objective: Because selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for depression, we investigated the effect of chronic treatment with the SSRI fluoxetine on long-term changes in CRF/CRF1 signaling in animals showing a depressive-like behavior., Methods: Male Wistar rats were exposed to the learned helplessness paradigm (LH). After evaluation of behavioral impairment, the animals were treated with fluoxetine (10 mg/kg i.p.) or saline for 21 days. We measured BLA CRF expression with RT-PCR and CRF1 expression in CA3 and the dentate gyrus of the hippocampus with in situ hybridization. We also studied the activation of one of CRF1's major intracellular signaling targets, the extracellular signal-related kinases 1 and 2 (ERK1/2) in CA3., Results: In saline-treated LH animals, CRF expression in the BLA increased, while hippocampal CRF1 expression and ERK1/2 activation decreased. Treatment with fluoxetine reversed the changes in CRF and CRF1 expressions, but not in ERK1/2 activation., Conclusion: In animals exposed to the learned helplessness paradigm, there are long-term changes in CRF and CRF1 expression that are restored with a behaviorally effective antidepressant treatment.

The term dysthymia is applied to a clinical picture characterized by depressive feelings of low intensity and chronic evolution. Psychiatric nosology includes it among the mood disorders or among neurosis and personality disorders. This ambiguity has empirical consequences, since bibliography examining the efficacy of the different treatments is relatively scarce, in particular if we consider the incidence of the dysthymic disorder, that rounds 3% of general population. In this work the history of the nosology of dysthimia, the efficacy of pharmacological approaches and a brief mention about the efficacy of adding psychotherapy are summarized. Current literature indicates that antidepressants, independently of the group they form part of, are better than placebo, that maintenance treatment should be recommended and that psychotherapy could bring an additional benefit.

This work summarizes the efforts made in the last twenty years towards the discovery of the physiopathogeny of mental diseases. It takes the "case" of major depression and reviews the different theories proposed to explain its physiopathogeny beginning with the role of excitatory aminoacids, glucocorticoids and trophic neurofactors in the '90s, the neurogenesis at the beginning of '00s and the genetics, the epigenetics and the research on neural networks in the last years. Result of these scientific efforts seem to be a construction which has at the same time the strength of the evidences employed in its building and the weakness that emerges from the reductionism necessary to obtain them.

We show the results of a survey on bipolar depression treatment using a sample of 359 argentine psychiatrists in the context of The National Psychiatry Congress that took place in the City of Buenos Aires, between September 26th and 29th, 2007. The objective was to study the attendant psychiatrists' prescribing habits in the treatment of bipolar depression. The discussion is based on the comparison between the answers and the recommendations taken from the main consensus, guidelines and from articles published by experts. The differences found point to the distance often present between guidelines and expert consensus series (based on patients meeting the strict criteria used in randomized controlled studies) on one hand, and a clinician's everyday real world practice, on the other hand.

This work summarizes the efficacy of pharmacotherapy in the chronic course of schizophrenia and unipolar depresion. It is aimed to answer three questions: does it cure these diseases? Does it exert any significant effect on the symptomatic presentation of the disorders? Which is its action on the social dysfunction provoked by schizophrenia or depression? A conceptual analysis of available bibliography was performed. It could be concluded that antypsychotics improve the symptomatic course of schizophrenia, although their efficacy is limited, and that these drugs does not act on the social dysfunction provoked by the disease. With respect to depression, it could be concluded that a significant proportion of patients remain symptomatic despite receiveng adequate treatments. No data about efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression is available.

Dysfunction of hippocampal plasticity has been proposed to play a critical role in the pathophysiology of depression. However, antidepressant drug effects on synaptic plasticity and cytoskeletal remodeling remain controversial. The aim of the present study was to evaluate in animals exposed to the learned helplessness (LH) paradigm, an accepted experimental model of depression, the effect of chronic treatment with fluoxetine (FLX) on synaptic and cytoskeletal proteins known to undergo plastic changes. Synaptophysin (SYN), postsynaptic density 95 (PSD-95), axon growth-associated protein 43 (GAP-43), and cytoskeletal proteins (intermediate neurofilaments and MAP-2) were studied in the hippocampus by immunohistochemistry. Whereas LH animals treated 21 days with saline (LH-S group) displayed diminished SYN and PSD-95 immunostainings in the CA3 but not in the DG, chronic treatment with FLX not only reversed the despaired behavior induced by exposure to LH paradigm, but also fully recovered SYN and PSD-95 labeling to control values. Similar results were obtained for the axonal remodeling marker GAP-43. FLX treatment did not modify either the decreased light neurofilament subunit (NFL) observed in the hippocampus of LH animals or any other cytoskeletal protein studied. When FLX treatment was withdrawn for 90 days in those LH-FLX animals in which reversion of despair had been observed at day 25, recurrence of despaired behavior was found accompanied by decreased SYN, PSD-95, and NFL labelings. Results indicate that the synapse remodeling induced by FLX in the CA3 region could underlie its behavioral efficacy despite the absence of cytoskeletal remodeling and that the stability of synaptic changes would depend on the continuous administration of the drug.

This work postulates the thesis that the development of the contemporary psychopharmacology, which began with the chemical changes imposed to molecules with antihistaminergic properties, modelled the current ethiopatogenic theories of mental diseases. The development of chlorpromazine and imipramine was coincident with the beginning of the research about neurotransmission. This coincidence contributed for the construction of the dopaminergic theory of schizophrenia and in the monoaminergic theory of depression. Limitations of the effectivity of current drugs, as observed in the trials CATIE and STAR-D may justify a change of perspective in the search for new molecular targets for the treatment of both diseases. Historical data are provided to illustrate the above mentioned thesis, in the perspective of two epistemological concepts: the context of discovery proposed by Hans Reichenbach and the epistemological obstacle, proposed by Gaston Bachelard.

Background: Atrophy of pyramidal hippocampal neurons and of the entire hippocampus has been reported in experimental models of depression and in depressive patients respectively. We investigated the efficacy of valproic acid (VPA) for reversing a depressive-like behaviour and a cytoskeletal alteration in the hippocampus, the loss of the light neurofilament subunit (NF-L)., Methods: Depressive-like behaviour was induced by inescapable stress. Animals were divided into four groups: two to assess the response to 21 days of treatment with 200 mg/kg (I.P.) of valproic acid, and two in which the treatment was interrupted and the effects of VPA were evaluated 90 days later. Depressive-like behaviour was evaluated by the quantification of escape movements in a swimming test. NF-L was quantified by immunohistochemistry in dentate gyrus and CA3 of hippocampus., Results: VPA corrected the depressive-like behaviour and reversed the diminution of NF-L in the hippocampus. Ninety days after the end of the treatment, and in contrast to the results previously obtained with fluoxetine, no recurrence of the depressive-like behaviour was observed., Conclusions: Despite interruption of the treatment, a long-lasting effect of VPA was observed. A possible relationship between the effect on NF-L and the prevention of depressive-like behaviour recurrence could be suggested.

Objective: The objective of this study was to examine the prescribing practices of Argentinean psychiatrists in the treatment of major depression and to observe similarities and/or differences with some consensus or treatment guidelines., Methodology: Four hundred two psychiatrists were surveyed during a specialty meeting in October 2005., Results: A total of 88.2 % of psychiatrists surveyed considered that every depressed patient must be treated with medication. The most prescribed antidepressants for outpatients were paroxetine, sertraline and fluoxetine. Venlafaxine was included for inpatients. The majority of psychiatrists indicated antidepressant therapy lasting from 12 to 24 months after remission of the first depressive episode. Antidepressant dosages remained unchanged during that period. A low percentage had used lithium or thyroid hormones as augmentation medications, the addition of other antidepressant being the most used augmentation strategy. The most prescribed antidepressant combination was dual antidepressants and SSRIs. Prescribing practices differed according to personal factors of the physicians., Conclusions: Discrepancies between clinical practice and treatment guidelines were observed. Further research over the underlying causes of these discrepancies and mechanisms to reduce them are necessary.

Hypercortisolism is a common trait of Cushing's disease and depression. These two disorders also share hippocampal volume decrease and cognitive deficits. However, experimentally induced hypercortisolism induces neuronal atrophy, which has been proposed to be the phenomenon underlying the hippocampal shrinkage. We hypothesized that the above-mentioned atrophy is due to a deleterious effect of high concentrations of glucocorticoids on cytoskeletal proteins. One or two pellets (100 mg each) of corticosterone were subcutaneously implanted in adult rats. Twenty-one days later, light, medium and heavy subunits of intermediate neurofilaments (NFL, NFM and NFH) and the microtubule-associated protein 2 (MAP2) were quantified by immunohistochemistry in Ammon's horn and dentate gyrus. We also evaluated the in vitro glutamate release in hippocampal slices. Both doses of corticosterone induced a decrement of NFL, NFM and NFH in both hippocampal areas but only 200 mg decreased MAP2. This dose also diminished the potassium-stimulated glutamate release. All of these changes seemed not to be due to neuron loss, as no decrement in neuron-specific nuclear protein-positive cells was found. With the exception of NFL, the above-mentioned diminution was not observed in the globus pallidus, one of the brain regions with the lowest glucocorticoid receptor density. These results provide a subcellular insight into the trophic changes found in experimental models of hypercortisolism. The coincidence between decrements in MAP2 and glutamate release suggests possible links between high glucocorticoid levels, dendritic atrophy and the cognitive impairment reported in patients suffering from Cushing's disease and depression.

In the last years efflux transporters, as for example P-glycoprotein, have been shown to play an important role in the regulation of the uptake of drugs in the central nervous system. These transporters are expressed constitutively in the brain capillary endothelial cells which form the brain-blood barrier, but their expression or activity could be inhibited or induced by other compounds or could be modified under pathological conditions. Some antipsychotics (amisulpride, chlorpromazine, fluphenazine, haloperidol, olanzapine, pimozide, prometazine, quetiapine, risperidone, trifluoperazine), antidepressants (amitriptiline, doxepine, nortriptiline, venlafaxine), and antiepileptics (felbamate, gabapentin, lamotrigine, phenobarbital and topiramate) are P-glycoprotein substrates. Interactions that could take place at the P-glycoprotein level may explain some cases of resistance in polimedicated patients. Other factors, yet unknown, could induce the expression of this transporter and therefore decrease the uptake of psychotropic drugs in the central nervous system, affecting their efficacy.

Either as a symptom or as a trait of an axis I disorder, anxiety is frequently associated with depressive episodes. Its treatment depends mainly of the syndrome in which it is included. While the selective serotonin reuptake inhibitors seem to be indicated in depression with comorbid anxiety disorders and in anxious depression, in agitated depression may be preferable to indicate mood stabilizers or sedative antipsychotics. Benzodiazepines may be useful at the beginning of the treatment of these special forms of depression, but it is advisable to tapper them off once the affective and/or the anxiety disorders improve.

This work summarizes the difficulties and aims of psychotropic administration in the treatment of mental disorders. The results of a survey about attitudes of psychoanalysts of the main psychoanalytic institutions in Argentina towards indications and objectives of psychotropic drugs use in psychoanalytic patients are summarized. Neurosciences attempts to build a bridge to connect biological and psychological and psychoanalytic knowledge, but for this efforts to be fruitful the non-dogmatic participation of professionals from the mind sciences may be necessary.

Benzodiazepines are anxiolytic, anticonvulsant, sedative and hypnotic compounds usually prescribed on a long-term basis. Chronic treatment with these compounds induces tolerance, which has been extensively attributed to modifications in the GABAergic neurotransmission. However, a compensatory increase in the excitatory response, named as an oppositional response, has also been put forward as a means for explaining such tolerance. Changes in the excitatory neurotransmission have been found in withdrawn rats after a long treatment with benzodiazepines but these modifications have not been conclusively studied during tolerance. In this work we studied several parameters of the glutamatergic neurotransmission in rats made tolerant to the sedative effect of 3 mg/kg (i.p.) of lorazepam (LZ). We found a decrease in the affinity of cortical NMDA receptors for (3)H-glutamate (K(D): 124.4 +/- 13.3 nM in tolerant rats, 71.6 +/- 10.4 nM in controls, P<0.05) together with a decrease in the in vitro 60 mM K(+)-stimulated cortical glutamate release (59+/- 12% vs. 153 +/- 38%, tolerant rats vs. controls, P<0.05). We conclude that tolerance to the sedative effect of LZ correlates with a decreased sensitivity for glutamate that may in turn diminish the cortical response to a chemical stimulus. Our findings constitute an evidence against the oppositional model of pharmacodynamic tolerance in this experimental condition.

This work reviews the cellular mechanisms, and the cerebral areas and circuits participating in the consolidation of episodic memory. At the cerebral level the circuit which connects the primary sensory cortices with the polimodal cortices, the entorhinal cortex, dentate gyrus, hippocampus and associative cortices is sequentially activated when the consolidation of a mnesic trace takes place. Cellular phenomena associated with this process is the long-term potentiation (LTP) which requires the activation of NMDA and AMPA receptors, the uptake of calcium and the activation of several enzymes which on one hand catalize the synthesis of retrograde messengers as nitric oxide and on the other induce genomic changes with trophic consequences for both the post and the presynaptic neurons. Eventual relationships between neurobiological findings and mnesic phenomena observed in psychoanalytic practice should be further investigated.

Excitatory amino acids (EAA) became known as neurotransmitters of the central nervous system (CNS) in the last decade. The most studied EAA are glutamate and aspartate. Both are synthetized by the same mechanism as gamaaminobutyric acid. (Fig. 1). Glutamate is widely distributed in the CNS and the spinal cord, being the areas of higher concentration the cerebral cortex, the hypocampus and the cerebellum. There have been identified two type of receptors for glutamate: ionotropic and metabotropic. The former includes three different types: NMDA, AMPA and KA. NMDA receptor is coupled to a Na+ and Ca2+ channel being the second ion the most important one. This receptor has several sites of binding for various substances. Along with the site for N-methyl-D-aspartate, which binds glutamate and/or aspartate, there have been identified a site for the binding of glycine (which is different from the strychnine sensitive one), a site for poliamines such as spermine and spermidine, and a site for the binding of Zn2+ (Table 1). AMPA receptor is associated to a Ca(2+)-Na+ channel, being in this case the Na+ the most important ion. There are two metabotropic type receptors: L-AP4 and trans-ACPD. Both are coupled to a G protein and agonists exert their action increasing phospholipase C activity which in turn induces an increment of IP3 and diacyl-glicerol, and a consecutive releasing of Ca2+ from intracellular stores. EAA play a role in some physiological processes. One of them is long-term potentiation (LTP), an electrochemical phenomenon involved in memory consolidation. Antagonists of NMDA and AMPA receptor prevent the development of LTP, and conversely, the agonist of glycine site of NMDA receptor--D-cycloserine--facilitates memory consolidation. Since 1957, EAA are considered neurotoxic substances and there are many indirect evidences to support this statement. Pathogenesis of neuronal damage elicited by EAA involves the events shown in Fig. 3. Prevention of the cascade of events that provokes neurotoxicity may be achieved by NMDA antagonists, but once it has begun it may be only aborted subtracting the Ca2+ from the medium, using nifedipine or blocking AMPA receptor with an antagonist (CNQX). EAA have been shown to play a toxic role in neuronal damage induced by ischemia. Research using various experimental models demonstrated that NMDA receptor antagonists (i.e. MK 801) blocks postischemic damage. Interventions at various levels of the pathogenic cascade shown in Fig. 4 provoke the same results. There is enough evidence to suspect that NMDA and AMPA receptors are altered in epilepsy. NMDA antagonists (i.e. MK801 or AP5) prevent the development of epileptic seizures induced by kindling; CNQX, an AMPA antagonist, blocks the increase in electrical activity induced by K+ in slices of hypocampus; felbamate, an antiepileptic drug, blocks the glycine site (not strychnine sensitive) decreasing NMDA receptor activity. Several neurodegenerative disorders have been associated with exogenous administration or accidental intake of EAA. (i.e. neurolatirism, Guam disease). Similarities between these diseases and lateral aminotrophic sclerosis indicate that in the latter EAA may play a pathogenic role. Finally, the psychotomimetic effect of phencyclidine (an antagonist of NMDA receptor) suggests that in schizophrenia, together with dopaminergic neurotransmission impairment, some dysfunction of glutamate pathways may be present.

In 30 female patients undergoing elective cholecystectomy, we have compared the anxiolytic effect of diazepam 10 mg with placebo, using measurements of cardiovascular (arterial pressure and heart rate), biochemical (plasma concentrations of noradrenaline, adrenaline, cortisol and dopamine beta-hydroxylase), subjective (visual analogue scale) and behavioural (Hamilton anxiety test) variables. Pretreatment evaluation was carried out the day before surgery and post-treatment examination was performed 1.5-2 h after oral administration of premedication, immediately before transfer of patients to the operating room. We found that diazepam 10 mg had no significant effect on any of the measured variables.