Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir.

OBJECTIVE: To assess whether changes in antiretroviral drugs other than thymidine nucleoside reverse transcriptase inhibitors (NRTI) may have a body fat impact in HIV-infected patients with lipoatrophy. METHODS: Ninety-six-week phase IV, open-label, multicentre, pilot randomized trial. HIV-infected patients with moderate/severe lipoatrophy at one or more body sites despite long-term thymidine NRTI-free therapy were randomized to continue their efavirenz (EFV)-based antiretroviral regimen or to switch from EFV to lopinavir/ritonavir (LPV/r). The primary endpoint was the absolute change in limb fat mass measured by dual X-ray absorptiometry from baseline to 96 weeks. Changes in other body fat measurements, subjective perception of lipoatrophy, subcutaneous fat gene expression and plasma lipids were also assessed. RESULTS: Thirty-three patients (73% men, median age 52 years) were recruited. At 96 weeks, absolute limb fat mass increased in the LPV/r arm vs. the EFV arm (estimated difference +1082.1 g; 95% CI +63.7 to +2103.5; P = 0.04); this difference remained significant after adjustment by gender, age, fat mass, body mass index and CD4 cell count at baseline. Subjective lipoatrophy perception scores also improved in the LPV/r arm relative to the EFV arm. Adipogenesis, glucose and lipid metabolism, and mitochondrial gene expression increased in the LPV/r arm compared with the EFV arm at 96 weeks. HDL cholesterol decreased in the LPV/r arm relative to the EFV arm. CONCLUSIONS: Switching from EFV to LPV/r in HIV-infected patients with lipoatrophy may offer further limb fat gain beyond thymidine NRTI discontinuation, although this strategy decreased plasma HDL cholesterol and caused changes in subcutaneous fat gene expression that may be associated with increased insulin resistance.

Differential subcutaneous adipose tissue gene expression patterns in a randomized clinical trial of efavirenz or lopinavir-ritonavir in antiretroviral-naive patients.

Gene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P < 0.05). After 16 weeks of exposure to the drug regimen, transcripts of CEBP/A, ADIPOQ, GLUT4, LPL, and COXIV were significantly down-regulated in the EFV arm compared to the LPV/r arm (P < 0.05). Significant correlations were observed between LPL expression change and trunk fat change at week 16 in both arms and between CEBP/A or COXIV change and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered at ClinicalTrials.gov under identifier NCT00759070.).

Contribution of genetic background and antiretroviral therapy to body fat changes in antiretroviral-naive HIV-infected adults.

OBJECTIVES: To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infected patients prospectively followed up according to the initiation and the type of ART. METHODS: Fifty single nucleotide polymorphisms (SNPs) in 26 genes, associated with obesity, insulin resistance, lipid metabolism or lipodystrophy in previously published genetic studies, were assessed in ART-naive HIV-infected Caucasian patients divided into three groups: 24 (27%) did not start ART, 29 (32.6%) received zidovudine or stavudine and 36 (40.4%) received neither zidovudine nor stavudine in their initial regimen. Patients underwent body fat measurements (using dual-energy X-ray absorptiometry) at baseline and Month 12. A multivariate model using backward stepwise elimination was used to assess the influence of SNPs and baseline levels of non-genetic covariates on changes in limb or trunk fat. RESULTS: The baseline characteristics were: 73% men, 17% coinfected with hepatitis C virus and/or hepatitis B virus, median age 37 years, median CD4+ T cell count 228/mm(3), median HIV-RNA 5.2 log copies/mL, median plasma glucose 85 mg/dL, median plasma insulin 9.1 IU/mL, median limb fat 5.6 kg and median trunk fat 7.0 kg. There were no baseline differences among the three groups except for the CD4+ T cell count. The decrease in limb fat was greater in the no-ART group relative to the other two groups (P < 0.05). The multivariate model showed associations of rs1801278 in IRS1 (P = 0.029, OR = 0.13), baseline viral load (P = 0.006; OR = 4.453) and baseline glucose levels (P = 0.008, OR = 0.926) with loss of limb fat, and rs2228671 in LDLR (P = 0.012, OR = 0.108), rs405509 in APOE (P = 0.048, OR = 0.205), baseline viral load (P = 0.005, OR = 0.186) and baseline CD4+ T cell count (P = 0.01, OR = 1.008) with gain of trunk fat. CONCLUSIONS: Specific polymorphisms in IRS1 (limb fat loss) and LDLR and APOE (trunk fat gain) were identified as independent markers of fat changes irrespective of the initiation of ART and the type of ART and deserve further validation.

High rate of autonomic neuropathy in Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. METHOD: Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. RESULTS: Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. CONCLUSIONS: Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

Water safety plan enhancements with improved drinking water quality detection techniques.

Drinking water quality has been regulated in most European countries for nearly two decades by the drinking water directive 98/83/EC. The directive is now under revision with the goal of meeting stricter demands for safe water for all citizens, as safe water has been recognized as a human right by the United Nations. An important change to the directive is the implementation of a risk-based approach in all regulated water supplies. The European Union Framework Seventh Programme Aquavalens project has developed several new detection technologies for pathogens and indicators and tested them in water supplies in seven European countries. One of the tasks of the project was to evaluate the impact of these new techniques on water safety and on water safety management. Data were collected on risk factors to water safety for five large supplies in Denmark, Germany, Spain and the UK, and for fifteen small water supplies in Scotland, Portugal and Serbia, via a questionnaire aiming to ascertain risk factors and the stage of implementation of Water Safety Plans, and via site-specific surveys known as Sanitary Site Inspection. Samples were collected from the water supplies from all stages of water production to delivery. Pathogens were detected in around 23% of the 470 samples tested. Fecal contamination was high in raw water and even in treated water at the small supplies. Old infrastructure was considered a challenge at all the water supplies. The results showed that some of the technique, if implemented as part of the water safety management, can detect rapidly the most common waterborne pathogens and fecal pollution indicators and therefore have a great early warning potential; can improve water safety for the consumer; can validate whether mitigation methods are working as intended; and can confirm the quality of the water at source and at the tap.

Assessment of radon risk areas in the Eastern Canary Islands using soil radon gas concentration and gas permeability of soils.

The Basic Safety Standard (BSS) Directive 2013/59/EURATOM of the European Union (EU) has stated the need for member states to establish national action plans to mitigate their general population's long-term risks of exposure to radon gas. Maps of radon-prone areas provide a useful tool for the development of such plans. This paper presents the maps of radon-prone areas in the Eastern Canary Islands (Gran Canaria, Fuerteventura and Lanzarote) obtained from assessment of Geogenic Radon Potential (GRP) distribution in the territory. GRP constitutes a magnitude that is contingent on both radon activity concentration and gas permeability of soils. An extensive campaign covering all geological formations of the Eastern Canary Islands was undertaken to locally sample these parameters. Geostatistical analysis of the spatial distribution of radon concentration in soils, permeability and GRP was performed on each of the islands, and the relationship between these magnitudes and the characteristic geological formations of the volcanic islands was investigated. Areas dominated by basic volcanic and plutonic rocks (originated by both recent and ancient volcanism) exhibit relatively low levels of radon in soils, and with the exception of specific cases of very high permeability, these areas are not classified as prone to radon risk according to international criteria. Areas in which intermediate or acidic volcanic and plutonic rocks predominate are characterised by greater radon activity concentration in soils, rendering them radon-prone. Given these results, Lanzarote is classified as an island with low radon risk all over its surface; Fuerteventura presents low-medium risk; and Gran Canaria contains extensive areas in the centre and north where the risk is medium or high. This classification is consistent with the risk maps obtained by National and European agencies from indoor radon measurements conducted on these islands.

Natural radioactivity in algae arrivals on the Canary coast and dosimetry assessment.

Nowadays, the use of wild and culture harvest seaweed in food industry is a booming productive sector. In this context, a radiological characterization of five globally common seaweed species that were collected in arrival on Gran Canaria coast was carried out. The studied algae species were Cymopolia barbata, Lobophora variegata, Sargassum vulgare, Dictyota dichotoma and Haliptilon virgatum. Radionuclides analysed by alpha and gamma spectrometry were 238U, 234U, 235U, 210Po, 234Th, 226Ra, 210Pb, 228Th, 224Ra, 40K and 7Be. Activity concentrations, ratios, and concentration factors (CF) were determined for all samples collected. The CF in algae was higher for reactive-particle radionuclides (210Po, 234Th, 228Th and 210Pb) than for conservative ones (40K and the uranium isotopes). 210Po, 228Th and 234Th CF were one or two orders of magnitude higher than those recommended by the IAEA. L. variegata, C. barbata and S. vulgare showed a clear preference for 210Pb and 210Po, for uranium radioisotopes, and for 40K and 234Th, respectively. A dosimetry assessment due to seaweed ingestion showed considerable values of annual committed effective dose for H. virgatum (605 ±â€¯19 µSv/y), L. variegata (574 ±â€¯17 µSv/y) and D. dichotoma (540 ±â€¯30 µSv/y). Hence, this study suggests that an algae radiological characterization is recommended as part of the product valorising process.

Comparing adaptation in emotional and non-emotional conflict in patients with schizophrenia and borderline personality disorder.

Research on conflict adaptation suggests that complex networks are involved in the detection and resolution of conflicts. These networks are believed to be different depending on whether the conflict occurs in emotional or non-emotional contexts. In addition, the adaptation to both types of conflict also seems to have different neural bases. The main aim of the present study was to compare conflict adaptation in two clinical groups - patients with schizophrenia (SZ) and patients with borderline personality disorder (BPD) - and a healthy control group during emotional and non-emotional versions of a facial Stroop task. We considered that the neural impairment and neuropsychological profile of these populations would be interesting to examine the above-mentioned mechanisms. Results showed that the performance was worse with incongruent compared to congruent stimuli in both task contexts. The Stroop effect was more marked in both clinical groups and greater in the SZ group. By contrast, the Gratton effect was clearly present in the SZ group, but was inverted in the BPD group mainly in the emotional task. Specifically, participants with BDP had a higher error rate in the current incongruent trial when the previous trial was incongruent in the emotional task. These results suggest that SZ and BDP groups have different patterns of conflict adaptation. Results are discussed according to the clinical characteristics and neural systems affected in each of these psychopathological disorders.

Mapping natural radioactivity of soils in the eastern Canary Islands.

The Canary Islands archipielago (Spain) comprises seven main volcanic islands and several islets that form a chain extending for around 500 km across the eastern Atlantic, between latitudes 27°N and 30°N, with its eastern edge only 100 km from the NW African coast. The administrative province of Las Palmas comprises the three eastern Canary Islands (Lanzarote, Fuerteventura and Gran Canaria). An extensive study of terrestrial gamma dose rates in surface soils has been carried out to cover the entire territory of the province (4093 km2). The average outdoor gamma dose rate in air at 1 m above ground is 73 nGyh-1 at Gran Canaria, 32 nGyh-1 at Fuerteventura, and 25 nGyh-1 at Lanzarote. To complete the radiological characterization of this volcanic area, 350 soil samples at 0-5 cm depth were collected to cover all the geologic typologies of the islands. These samples were measured using high resolution gamma spectrometry to determine the activity concentrations of 226Ra, 232Th and 40K. The average values obtained were 25.2 Bq/kg, 28.9 Bq/kg, and 384.4 Bq/kg, respectively. Maps of terrestrial gamma activity, effective dose, and activity concentrations of 226Ra, 232Th and 40K for the region have been developed through the use of geostatistical interpolation techniques. These maps are in accord with the geology of the islands.

Are executive functions related to emotional intelligence? A correlational study in schizophrenia and borderline personality disorder.

This research explored the relationship between executive functions (working memory and reasoning subtests of the Wechsler Adult Intelligence Scale, Trail Making and Stroop tests, fluency and planning tasks, and Wisconsin Card Sorting Test) and emotional intelligence measured by the Mayer-Salovey-Caruso Emotional Intelligence Test in patients with schizophrenia or borderline personality disorder compared to a control group. As expected, both clinical groups performed worse than the control group in executive functions and emotional intelligence, although the impairment was greater in the borderline personality disorder group. Executive functions significantly correlated with social functioning. Results are discussed in relation to the brain circuits that mediate executive functions and emotional intelligence and the findings obtained with other models of social cognition.

A simple methodology for characterization of germanium coaxial detectors by using Monte Carlo simulation and evolutionary algorithms.

The determination in a sample of the activity concentration of a specific radionuclide by gamma spectrometry needs to know the full energy peak efficiency (FEPE) for the energy of interest. The difficulties related to the experimental calibration make it advisable to have alternative methods for FEPE determination, such as the simulation of the transport of photons in the crystal by the Monte Carlo method, which requires an accurate knowledge of the characteristics and geometry of the detector. The characterization process is mainly carried out by Canberra Industries Inc. using proprietary techniques and methodologies developed by that company. It is a costly procedure (due to shipping and to the cost of the process itself) and for some research laboratories an alternative in situ procedure can be very useful. The main goal of this paper is to find an alternative to this costly characterization process, by establishing a method for optimizing the parameters of characterizing the detector, through a computational procedure which could be reproduced at a standard research lab. This method consists in the determination of the detector geometric parameters by using Monte Carlo simulation in parallel with an optimization process, based on evolutionary algorithms, starting from a set of reference FEPEs determined experimentally or computationally. The proposed method has proven to be effective and simple to implement. It provides a set of characterization parameters which it has been successfully validated for different source-detector geometries, and also for a wide range of environmental samples and certified materials.

HIV/antiretroviral therapy-related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma.

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

Lymphoid tissue viral burden and duration of viral suppression in plasma.

OBJECTIVES: To assess virological response in lymphoid tissue and its impact on the durability of response in plasma in HIV-1-infected persons who achieved sustained suppression of plasma viraemia with different antiretroviral regimens. METHODS: Consecutive patients on first-line antiretroviral therapy were included if they had a plasma HIV-1 RNA viraemia < 20 copies/ml within the last 6 months and tonsillar tissue accessible for biopsy. First-line therapy contained two nucleoside analogues: alone (2NRTI group, n = 3); plus a HIV-1 protease inhibitor (PI group, n = 11) or plus nevirapine (NVP group; n = 16). Patients were followed until virus was detectable in plasma, they changed therapy or were lost to follow-up. RESULTS: Tonsillar HIV-1 RNA could be detected (> 100 copies/mg) in 10 patients: one in the PI group (9%), six (38%) in the NVP group and in all three patients in the 2NRTI group. Primary resistance mutations could be detected in only 2 of these 10 patients. After a median of 9 months after the biopsies, viral suppression in plasma had failed in 6 of these 10 patients whereas failure had only occurred in 1 out of 20 with initially undetectable viral load in lymphoid tissue (P = 0.01; log rank test). CONCLUSIONS: In patients with sustained viral suppression in plasma, triple therapy including a HIV-1 protease inhibitor was more potent than triple therapy containing nevirapine or dual therapy with nucleoside analogues to reduce viral burden in lymphoid tissue. A worse response in lymphoid tissue could not be explained by local selection of resistance and was associated with a less durable virological response in plasma.

The virological and immunological consequences of structured treatment interruptions in chronic HIV-1 infection.

BACKGROUND: Some individuals with chronic HIV-1 infection have discontinued their drug therapy with consequent plasma virus rebound. In a small number of patients, a delayed or absent rebound in plasma virus load has been noted after drug cessation, apparently associated with prior drug interruptions and autologous boosting of HIV-1 specific immune responses. We hypothesized that cyclic structured treatment interruptions structured treatment interruptions (STI) could augment HIV-1 specific immune responses in chronic HIV-1 infection, which might help to control HIV-1 replication off therapy. METHODS: We initiated an STI pilot study in 10 antiretroviral treatment-naive HIV-1 chronically infected subjects with baseline CD4 T-cell counts > 500 x 10(6) cells/l and plasma viral load > 5000 copies/ml who received highly active antiretroviral therapy (HAART) for 1 year with good response (plasma viral load < 20 copies/ml for at least 32 weeks). Three cycles of HAART interruption were performed. RESULTS: In all of the patients viral load rebounded, but doubling times increased significantly between the first and third stops (P = 0.008), and by the third stop, six out of nine subjects had a virological set-point after a median 12 months off therapy that was lower than baseline before starting HAART (ranging from 0.6 log(10) to 1.3 log(10) lower than baseline) and in four it remained stable below 5000 copies/ml. Those subjects who controlled viral replication developed significantly stronger HIV-1 specific cellular immune responses than subjects lacking spontaneous decline (P < 0.05). During viral rebounds no genotypic or phenotypic changes conferring resistance to reverse trancriptase inhibitors or protease inhibitors was detected, but mean absolute CD4 T-cell counts declined significantly, although never below 450 x 10(6)/l and the mean value at 12 months off therapy was significantly higher than the pre-treatment level (P = 0.004). CONCLUSIONS: Our findings suggest that STI in chronic HIV-1 infection might augment HIV-1-specific cellular immune responses associated with a spontaneous and sustained drop in plasma viral load in some subjects but at the potential cost of lower CD4 T-cell counts.

Electrical intracerebral stimulation of the area postrema on taste aversion learning.

The structural characteristics of the area postrema, its anatomical connections, participation in the detection of emesis-provoking substances and the effects of area postrema lesions on taste aversion learning acquisition, are all factors which speak in favor of a role as a chemoreceptor zone involved in the detection of aversive agents which act as effective inducers of taste aversion learning. The feasibility of substituting electrical intracerebral stimulation of the area postrema for the aversive stimulus was investigated in a taste aversion learning paradigm. In Expt. 1, 0.1-ms rectangular pulses of 50 Hz, delivered intermittently or continuously for 4 h after a 15-min delay following ingestion of the gustatory stimulus, produced reliable learning. Expt. 2 showed the learning thus induced to reflect all the characteristics features attributed to taste aversion learning: one-trial learning, long interstimulus delay and cue-consequence specificity. These results suggest that the area postrema could participate in the detection of the aversive consequences of particular taste aversion learning-inducing agents.

Participation of the area postrema in learned aversions induced by body rotation.

Existing data on the effects of area postrema (AP) lesions on body rotation-induced emesis as well as on the participation of this zone in the acquisition of taste aversion learning (TAL) with other emetic agents suggest a possible role for the AP in learned aversions induced by body rotation. Nevertheless, earlier studies have shown that AP lesions do not prevent learned aversions induced by body rotation. The present experiments were performed in male Wistar rats in order to explore the effects of AP lesions on body rotation-induced flavor aversions as a function of the paradigm employed. Flavor aversions were induced by 30 min of circular body rotation (90 r.p.m.) using two different paradigms: a standard one including one trial learning, delay and single stimulus test and a three trials paradigm (with and without interstimulus delay) including both single stimulus test and choice test. AP lesions disrupt acquisition provided that the paradigm used includes interstimulus delay, i.e. when body rotation is applied 15 min after flavor intake. However, the AP seems to play no essential role when body rotation is applied immediately after flavor intake in a three-trial paradigm, as no effects were observed following AP lesions. In addition, subdiaphragmatic vagotomy plus simultaneous AP lesions leads to no interference in the acquisition of learned aversions induced by body rotation applied immediately after intake. It is concluded that body rotation may trigger a variety of aversive effects capable of inducing learned aversions, each apparently involving independent neural systems.

Lesions of the lateral parabrachial nuclei disrupt aversion learning induced by electrical stimulation of the area postrema.

The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP.

Effects of medullary afferent vagal axotomy and area postrema lesions on short-term and long-term NaCl-induced taste aversion learning.

This series of experiments demonstrates a functional dissociation between the area postrema (AP) and the vagus nerve in short-term taste aversion learning (TAL). Although medullary axotomy of the afferent component of the vagus disrupted the learning observed with NaCl-induced short-term (nondelayed) TAL, lesioning the AP failed to interfere with the discriminative process employed by the animals under the same conditions. However, involvement of neither the vagus nerve nor the AP seemed to be indispensable for learning in NaCl-induced long-term (delayed) TAL. The possibility that the vagus nerve and the AP are involved in temporally distinct visceral processing is discussed.

The functional relevance of the lateral parabrachial nucleus in lithium chloride-induced aversion learning.

Lesions to the lateral parabrachial nucleus (PBN), one of the subnuclei that make up the pontine parabrachial complex, impairs the acquisition of taste aversion learning (TAL) with LiCl as the toxic stimulus. In this experiment, PBNl-lesioned and control rats were trained to learn a delayed task with a 15-min interval between presentation of the gustatory and the aversive stimulus. The impairment in learning observed after lesions of the PBNl is discussed in terms of disruption of the transmission of toxic stimuli (LiCl) processed by the humoral pathway and the area postrema (AP).

The functional relevance of the area postrema in drug-induced aversion learning.

Research into the neural mechanisms involved in the acquisition of learned aversions induced by drug points toward the area postrema (AP) as one of the structures implicated in the detection of drug aversive consequences. The evidence suggest that although the AP is indeed involved in drug-induced learned aversions, its functional integrity is not always a necessary requisite for learning to take place. The aim in this study was to determine whether the AP is essentially or selectively involved in all learned aversions induced by scopolamine methyl nitrate (SMN) using different number of trials with the aversive stimulus. In Experiment 1, AP-lesioned rats were injected with SMN fifteen minutes after consuming a flavoured solution during three consecutive trials. A single-stimulus test failed to detect learned aversions, which were, however, evident in two subsequent choice-tests. In one-trial paradigms, however, choice-tests as well as single-stimulus tests failed to detect learned aversions in AP-lesioned rats, both when SMN was injected immediately after stimulus intake (Experiment 2) and when a fifteen-minute delay was introduced (Experiment 3). The results suggested that the AP is not essential for the acquisition of SMN-induced aversion learning with three consecutive trials if learning is detected with a choice-test, although effective single-trial learning does apparently require a functional AP.