Constructed wetlands for combined sewer overflow treatment: A state-of-the-art review.

Combined sewer overflows (CSOs) are a major source of surface water pollution and degradation. This is particularly visible where sewage collection with combined sewer and centralized treatment are well established, such as in Europe and North America: an overwhelming number of surface water bodies are in insufficient status of ecology, hydrology and physico-chemical parameters. Therefore, several countries have started implementing constructed wetlands (CWs) as mainstream on-spot treatment. This paper summarizes the main design approaches that can be adopted. We identified eight different schemes for the implementation of CSO-CWs, based on our international experience and documented by a literature analysis. The performance review includes conventional water quality parameters, as well as pathogen and emergent contaminant removal. Furthermore, modelling tools for advanced design and for understanding a wide applicability of these green infrastructures are presented. This paper also provides a review on other side benefits offered by the adoption of Nature-Based Solutions for CSO treatment, such as ecosystem services, and the most common issues related to their operation and maintenance. Our analysis has produced a list of key factors for design and operation, all derived from full-scale installations in operation up to more than ten years.

Plasticity of the human visual brain after an early cortical lesion.

In adults, partial damage to V1 or optic radiations abolishes perception in the corresponding part of the visual field, causing a scotoma. However, it is widely accepted that the developing cortex has superior capacities to reorganize following an early lesion to endorse adaptive plasticity. Here we report a single patient case (G.S.) with near normal central field vision despite a massive unilateral lesion to the optic radiations acquired early in life. The patient underwent surgical removal of a right hemisphere parieto-temporal-occipital atypical choroid plexus papilloma of the right lateral ventricle at four months of age, which presumably altered the visual pathways during in utero development. Both the tumor and surgery severely compromised the optic radiations. Residual vision of G.S. was tested psychophysically when the patient was 7 years old. We found a close-to-normal visual acuity and contrast sensitivity within the central 25° and a great impairment in form and contrast vision in the far periphery (40-50°) of the left visual hemifield. BOLD response to full field luminance flicker was recorded from the primary visual cortex (V1) and in a region in the residual temporal-occipital region, presumably corresponding to the middle temporal complex (MT+), of the lesioned (right) hemisphere. A population receptive field analysis of the BOLD responses to contrast modulated stimuli revealed a retinotopic organization just for the MT+ region but not for the calcarine regions. Interestingly, consistent islands of ipsilateral activity were found in MT+ and in the parieto-occipital sulcus (POS) of the intact hemisphere. Probabilistic tractography revealed that optic radiations between LGN and V1 were very sparse in the lesioned hemisphere consistently with the post-surgery cerebral resection, while normal in the intact hemisphere. On the other hand, strong structural connections between MT+ and LGN were found in the lesioned hemisphere, while the equivalent tract in the spared hemisphere showed minimal structural connectivity. These results suggest that during development of the pathological brain, abnormal thalamic projections can lead to functional cortical changes, which may mediate functional recovery of vision.

Lessons learnt from a pilot study on residual dye removal by an aerated treatment wetland.

Treatment wetlands (TWs) have shown good capacity in dye removal from textile wastewater. However, the high hydraulic retention times (HRTs) required by these solutions and the connected high area requirements, remain a big drawback towards the application of TWs for dye treatment at full scale. Aerated TWs are interesting intensified solutions that attempt to reduce the TW required area. Therefore, an aerated CW pilot plant, composed of a 20 m2 horizontal subsurface flow TW (HF) and a 21 m2 Free Water System (FWS), equipped with aeration pipelines, was built and monitored to investigate the potential reduction of required area for dye removal from the effluent wastewater of a centralized wastewater treatment plant (WWTP). During a 8 months long study, experimenting with different hydraulic retention times (HRTs - 1.2, 2.6 and 3.5 days) and aeration modes (intermittent and continuous), the pilot plant has shown a normal biological degradation for organic matter and nutrients, while the residual dye removal has been very low, as demonstrated by the absorbance measure at three wavelengths: at 426 nm (blue) the removal varies from -55% at influent absorbance of 0.010 to 41% at 0.060; at 558 nm (yellow) the removal is negative at 0.005 (-58%) and high at higher influent concentrations (72% at 0.035 of absorbance for the inlet); at 660 nm (red) -82% of removal efficiency was obtained at influent absorbance of 0.002 and 74% at 0.010. These results are a consequence of the biological oxidation processes taking place in the WWTP, so that the residual dye seems to be resistant to further aerobic degradation. Therefore, TWs enhanced by aeration can provide only a buffer effect on peak dye concentrations.

The role of constructed wetlands in a new circular economy, resource oriented, and ecosystem services paradigm.

Wastewater management is included in one of the 17 Sustainable Development Goals (SDGs): SDG 6 is dedicated to water and sanitation and sets out to "ensure availability and sustainable management of water and sanitation for all". SDG 6 expands the Millennium Development Goals (MDGs) focus on drinking water and basic sanitation to now cover the entire water cycle, including the management of water, wastewater and ecosystem resources. A UN report in 2017 states that likely over 80% of the wastewater worldwide is still discharged without adequate treatment. In several countries the wastewater management is nowadays a norm, but still there are open discussions about the kind of approach to be adopted, i.e. centralisation vs. decentralisation. The choice of the adopted technologies is strictly linked to environmental performances and economical aspects; one of the possible causes for the still enormous amount of untreated wastewater discharged into the environment can be the low "willingness to pay" for this kind of service and therefore a great focus should be given to all the technologies that are able to lower the treatment costs still maintaining reliable and robust performances in the long term. When considering wastewater as a carrier of valuable primary chemicals that can be easily converted to marketable products (fertilisers, bio-plastics, soil conditioners, biofuels, etc.), and as well as a relevant source of "new water" to be used for specific purposes, wastewater and runoff management can be highlighted as one of the most exciting challenges and occasions for a sustainable development in the near future. The paper aims to clarify the future role of CWs in circular economy, resource-oriented, and ecosystem services approaches, which want to respond to sanitation worldwide and the future research needs. We give an overview on how the conventional wastewater treatment scheme (what we call "waste paradigm") should move towards more sustainable water and biogeochemical cycles following the new resource-oriented, circular economy and ecosystem service views. On this basis, we review the potential application of CWs within this new, and needed, paradigm. Finally, a meta-analysis shows that the scientific community involved in CWs should put more effort in making CWs more suitable for these new tasks.

Upflow anaerobic sludge blanket and aerated constructed wetlands for swine wastewater treatment: a pilot study.

Swine wastewater management is often affected by two main issues: a too high volume for optimal reuse as a fertilizer and a too high strength for an economically sustainable treatment by classical solutions. Hence, an innovative scheme has been tested to treat swine wastewater, combining a low cost anaerobic reactor, upflow anaerobic sludge blanket (UASB), with intensified constructed wetlands (aerated CWs) in a pilot scale experimental study. The swine wastewater described in this paper is produced by a swine production facility situated in North Italy. The scheme of the pilot plant consisted of: (i) canvas-based thickener; (ii) UASB; (iii) two intensified aerated vertical subsurface flow CWs in series; (iv) a horizontal flow subsurface CW. The influent wastewater quality has been defined for total suspended solids (TSS 25,025 ± 9,323 mg/l), organic carbon (chemical oxygen demand (COD) 29,350 ± 16,983 mg/l), total reduced nitrogen and ammonium (total Kjeldahl nitrogen (TKN) 1,783 ± 498 mg/l and N-NH4+ 735 ± 251 mg/l) and total phosphorus (1,285 ± 270 mg/l), with nitrates almost absent. The overall system has shown excellent performances in terms of TSS, COD, N-NH4+ and TKN removal efficiencies (99.9%, 99.6%, 99.5%, and 99.0%, respectively). Denitrification (N-NO3- effluent concentration equal to 614 ± 268 mg/l) did not meet the Italian quality standards for discharging in water bodies, mainly because the organic carbon was almost completely removed in the intensified CW beds.

Large scale application of French reed beds: municipal wastewater treatment for a 20,000 inhabitant's town in Moldova.

A two-stage vertical flow treatment wetlands system (French reed beds) was realized in 2012-2013 for the Orhei's town in Moldova. The treatment system occupies a total area of about 5 ha and operates in cold climate conditions during winter, with air temperatures below -20 °C. The first 2 years (2013-2015) of treatment performances for this system are presented here, with a particular highlight on the analysis of the commissioning phase and the operative choices taken along this period basing on the observed results. The specific classification of this application of constructed wetlands (CWs) for the primary and secondary treatment of municipal wastewater as a medium-large size system makes this technical report a relevant reference for demonstrating the possible extension to the highest numbers of inhabitants for the common application range of this family of technologies (CWs) for municipal wastewater. The observed performances for organic carbon (both as chemical oxygen demand (COD) and biochemical oxygen demand (BOD5)), suspended solids and ammonia removals in the whole first operational period consistently satisfied the national limits for discharge in rivers, respectively, with average values of 86%, 96% and 66%. The treated daily flow was measured in the range of 1,000-2,000 m3/d.

Wineries wastewater treatment by constructed wetlands: a review.

The application of wetland systems for the treatment of wineries wastewater started in the early 1990s in the USA followed a few years later by France, Italy, Germany and Spain. Various studies demonstrated the efficiency of constructed wetlands (CWs) as a low cost, low maintenance and energy-saving technology for the treatment of wineries wastewater. Several of these experiences have also shown lessons to be learnt, such as some limits in the tolerance of the horizontal subsurface flow and vertical subsurface flow classic CWs to the strength of the wineries wastewater, especially in the first stage for the multistage systems. This paper is presenting an overview of all the reported experiences at worldwide level during the last 15 years, giving particular attention and provision of details to those systems that have proven to get reliable and constant performances in the long-term period and that have been designed and realized as optimized solutions for the application of CW technology to this particular kind of wastewater. The organic loading rates (OLRs) applied to the examined 13 CW systems ranged from about 30 up to about 5,000 gCOD/m² d (COD: chemical oxygen demand), with the 80th percentile of the reported values being below 297 gCOD/m² d and the median at 164 gCOD/m² d; the highest OLR values have in all cases been measured during the peak season (vintage) and often have been linked to lower surface removal rates (SRRs) in comparison to the other periods of the year. With such OLRs the SRRs have ranged from a minimum of 15 up to 4,700 gCOD/m² d, with the 80th percentile of the reported values being below 308 gCOD/m² d and the median at 112 gCOD/m² d.

Multi-stage constructed wetland systems for municipal wastewater treatment.

In the present paper the detailed design and performances of two municipal wastewater treatment plants, a four-stage constructed wetlands (CW) system located in the city of Dicomano (about 3,500 inhabitants) in Italy, and a three-stage CW system for the village of Chorfech (about 500 inhabitants) in Tunisia, are presented. The obtained results demonstrate that multi-stage CWs provide an excellent secondary treatment for wastewaters with variable operative conditions, reaching also an appropriate effluent quality for reuse. Dicomano CWs have shown good performances, on average 86% of removal for the Organic Load, 60% for Total Nitrogen (TN), 43% for Total Phosphorus (TP), 89% for Total Suspended Solids (TSS) and 76% for Ammonium (NH4(+)). Even the disinfection process has performed in a very satisfactory way, reaching up to 4-5 logs of reduction of the inlet pathogens concentration, with an Escherichia coli average concentration in the outlet often below 200 UFC/100 mL. The mean overall removal rates of the Chorfech CWs during the monitored period have been, respectively, equal to 97% for TSS and Biochemical Oxygen Demand (BOD5), 95% for Chemical Oxygen Demand (COD), 71% for TN and 82% for TP. The observed removal of E. coli by the CW system was in this case 2.5 log units.

Complete Healing of a Giant Wart in a Severely Immune-Compromised Patient with HIV Infection Treated with Acupuncture.

Giant warts are infrequent dermatological viral infections caused by Papillomavirus (HPV) in immune-compromised patients. Treatment may often be difficult and unsatisfactory, either by surgery or cytotoxic agents, because of poor immune control of viral activity in such hosts. Here we report on the case of a patient with advanced and persistent immune suppression caused by HIV disease, who developed a monstrous wart covering the entirety of the radial district of his right hand. He was completely healed after a long treatment with traditional Chinese acupuncture, in spite of minimal immune recovery induced by efficacious antiretroviral therapy. To the best of our knowledge, therefore, the present report may be the first direct clinical evidence that acupuncture may be effective in the treatment of cutaneous warts also in HIV-infected patients.

Shelf life prediction of fresh Italian pork sausage modified atmosphere packed.

The shelf life of fresh Italian pork sausages packed in modified atmosphere was studied. Samples were packed using different levels of oxygen (high and low) with different levels of carbon dioxide (high-low) in the atmospheres headspace and were stored at 4 °C for 9 days. Microbial, physiochemical and sensory parameters were analyzed during storage. A consumer test was performed to determine the critical acceptability levels. Sensory data were mathematically modelled to estimate product shelf life. A first-order kinetic model and a Weibull-type model aptly described, respectively, the changes in fresh pork sausage odor and color over storage time. These models may be used to predict the sensory shelf life of fresh pork sausage. Results showed that 20% O(2) and 70% CO(2) extend fresh pork sausage shelf life to 9 days at 4 °C. The microbial quality of the samples at the critical sensory level of acceptability was within the range of microbial acceptability.

Treatment of segregated black/grey domestic wastewater using constructed wetlands in the Mediterranean basin: the zer0-m experience.

Concerns about water shortage and pollution have received increased attention over the past few years, especially in developing countries with warm climate. In order to help local water management in these countries, the Euro-Mediterranean Regional Programme (MEDA) has financed the Zer0-m project (E-mail: www.zer0-m.org). As a part of this project, several constructed wetland (CW) pilot systems with different pre-treatments have been implemented in four Technological Demonstration Centres in Egypt, Morocco, Tunisia and Turkey. The aim of this research was to establish appropriate designs for treatment of segregated domestic black (BW) and grey water (GW). We tested several different multistage CW configurations, consisting of horizontal and vertical subsurface flow CW for secondary treatment and free water systems as tertiary stage. CW removal efficiencies of TSS, COD, BOD(5), N-NH(4)(+), N-NO(3)(-), N(tot), total coliforms (TC) were evaluated for each of the implemented systems. The results from this study demonstrate the potential of CWs as a suitable technology for treating segregated domestic wastewater. A very efficient COD reduction (up to 98%) and nitrification (92-99%) was achieved for BW and GW in all systems. CW effluent concentrations were below 15 mg/L for BOD(5), 1 mg/L for N-NO(3)(-) and 0.5 mg/L for N-NH(4)(+) together with acceptable TC counts. Based on these results, we suggest adopting the design parameters used in this study for the treatment of segregated wastewater in the Mediterranean area.

Efficacy and safety of a salvage regimen based on tipranavir, enfuvirtide and three nucleoside analogues in HIV1 infected patients with clinical progression: 96-week evaluation.

In recent years, novel antiretroviral drugs have become available for multi-experienced HIV-infected patients with limited options. We enrolled seven advanced HIV-patients, failing multiple previous HAART regimens, in virological failure on their current HAART regimen and showing recent clinical and immunological progression. All patients were prescribed a double-boosted tipranavir plus enfuvirtide based regimen, in addition to zidovudine, tenofovir and lamivudine for salvage therapy. To assess susceptibility to tipranavir, the tipranavir genotypic resistance score was calculated and two years later this was re-evaluated on an updated tipranavir genotypic score algorithm. At baseline, CD4 were 139/mcL (more or less 145), HIV-1 RNA was 822,700 cp/mL. All patients achieved HIV-1 RNA levels less than 400 cp/mL between 12 weeks and 24 weeks of observation; two reached less than 50 cp/mL during this period. At 48 weeks three patients had reached less than 50 cp/mL; three other patients had HIV RNA less than 200 cp/mL. At 72 and 96 weeks HIV viraemia was less than 50 cp/mL in six patients; CD4 T-cell counts 285/mcL (more o less 198). No AIDS-defining events were recorded. Adverse events did not need to stop or change HAART. Strong 3 NRTI backbone could help efficacy and durability, and frequent evaluations in complex patients can help to manage toxicity.

Tolerance to hydraulic and organic load fluctuations in constructed wetlands.

This paper describes a two-year performance evaluation of four different constructed wetland (CW) treatment systems designed by IRIDRA Srl, located in central Italy. All four CW systems were established to treat wastewater effluent from different tourist activities: (1) one single-stage CW for secondary treatment of domestic wastewater (30 p.e.) at a holiday farm site; (2) a hybrid compact system consisting of two stages, a horizontal flow (HF) system followed by a vertical flow (VF) system for the secondary treatment of effluent from a 140 p.e. tourist resort; (3) a single-stage vertical flow (VF) CW for a 100 p.e. mountain shelter; and (4) a pair of single-stage, HF CWs for the secondary treatment of segregated grey and black water produced by an 80 p.e. camping site. These tourism facilities are located in remote areas and share some common characteristics concerning their water management: they have high variability of water consumption and wastewater flow, depending on the season, weather and weekly regularities; they have no connection to a public sewer and most sites are located in a sensitive environment. Total suspended solids (TSS), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), ammonium (N-NH4+), nitrate (N-NOx), total nitrogen (Ntot), total phosphorus (Ptot), total coliform (TC), faecal coliform (FC), E. coli removal efficiencies for all four CW systems are presented. The results from this study demonstrate the potential of CWs as a suitable technology for treating wastewater from tourism facilities in remote areas. A very efficient COD reduction (83-95%) and pathogen elimination (3-5 logs) have been achieved. Furthermore, the CWs are easily maintained, robust (not sensitive to peak flows), constructed with local materials, and operate with relatively low cost.

Microcirculation as a novel marker of membrane biocompatibility.

BACKGROUND: It is possible to consider microcirculation as a kind of OwitnessO of the complex biological reactions triggered by the dialytic treatment. The reactivity of microcirculation to the dialytic stress may represent a measure of the overall biocompatibility of the membrane. In this study we tested the hypothesis that different synthetic membranes may have different biological effects, particularly related to microcirculation. SUBJECTS AND METHODS: In this crossover study, we observed 16 chronically hemodialyzed patients. All patients were treated with the EVAL membrane; we recorded the TcPO2 during the second treatment of the week. All patients were then switched to the hf-PS membrane. During the study observation we did not change the dialytic prescription or the pharmacologic treatment. RESULTS: From the beginning of the session until 90O, the behavior of TcPO2 is similar for both the membranes. From 120O to the end of the treatment in sessions with the EVAL membrane, the TcPO2 values come back to the starting level, whereas in the treatments with hf-PS the TcPO2, the values remain at a lower level; there was a significant difference between EVAL and hf-PS in the values recorded. Arterial blood gas values of paO2 and paCO2 are quite similar in the treatments with both the membranes, without any significant difference. CONCLUSIONS: The analysis of microcirculation by means of TcPO2 measurement is a useful tool to obtain a OclinicalO measure of biocompatibility of the dialytic treatment and different membranes may have different impacts on TcPO2.

Acquisition of a palatable-food-sustained appetitive behavior in satiated rats is dependent on the dopaminergic response to this food in limbic areas.

Rats exposed to repeated unavoidable stress show decreased dopamine output in the nucleus accumbens shell (NAcS) and do not acquire vanilla sugar (VS)-sustained appetitive behavior (VAB). Rats treated with lithium for 3 weeks also show decreased NAcS dopamine output, yet they acquire VAB. Feeding a novel palatable food increases extraneuronal dopamine levels in the NAcS and medial prefrontal cortex (mPFC) in rats. In order to investigate the role of food-induced dopamine release in VAB acquisition, we studied by microdialysis the dopaminergic response in the NAcS and mPFC to the presentation and consumption of VS in satiated control rats, and in satiated rats exposed to repeated stress or lithium treatment. The dopaminergic response to VS was also studied in rats familiar with VS, or that had acquired VAB. In control rats, VS feeding was accompanied by increased dopamine output in the NAcS and mPFC, and one-trial habituation to this effect developed in the NAcS. Rats exposed to a 7-day stress showed reduced interest in VS pellets, and when fed VS they did not show a dopaminergic response in the NAcS and mPFC. Lithium-treated rats rapidly ate VS pellets and showed increased dopamine output in the NAcS and mPFC, with no habituation in the NAcS response. Rats familiar with VS and rats that had already learned VAB ate VS pellets. The first group showed a lower dopaminergic response to VS consumption than the control group, but the latter showed no dopaminergic response in the NAcS and mPFC. We propose that the limbic dopaminergic response to a novel palatable food plays a role in associative learning and that it is predictive of the competence to learn an appetitive behavior. Moreover, in our experimental conditions a phasic increase in mesolimbic dopamine no longer signals the VS stimulus once it has become a reinforcer in an appetitive task.

Dizocilpine infusion has a different effect in the development of morphine and cocaine sensitization: behavioral and neurochemical aspects.

The stimulation of glutamate receptors plays a relevant role in the development of behavioral sensitization to psychostimulants, while less clear results have been obtained on their role in morphine sensitization. We addressed this issue by comparing the development of cocaine and morphine sensitization under a continuous s.c. infusion of the N-methyl-D-aspartate (NMDA) antagonist dizocilpine (0.1 mg/kg/24 h). Moreover, we studied the expression of NMDA and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunits in discrete limbic areas of rats sensitized to morphine or cocaine with or without the concomitant dizocilpine infusion. It was observed that dizocilpine infusion did not prevent the development of morphine sensitization, while it prevented the development of tolerance to morphine-induced analgesia. Finally, morphine-sensitized animals did not present any modification in the subunit expression of glutamate receptors in the brain areas examined. In agreement with previous results, we found that dizocilpine infusion prevented the development of cocaine sensitization. Moreover, we observed that rats sensitized to cocaine presented a significant increase in the levels of GLUR1, NR1 and NR2B, in the nucleus accumbens, and of NR2B in the hippocampus compared to control animals. Such modifications were absent in rats administered cocaine under dizocilpine infusion. We conclude that: (i) morphine sensitization is a neuroadaptive phenomenon which does not appear to require NMDA receptor activity in order to develop; (ii) cocaine sensitization is clearly dependent on NMDA receptor activity, as dizocilpine infusion prevented the occurrence of glutamate receptors modifications as well as the development of sensitization.

Long-term behavioral and neurochemical effects of chronic stress exposure in rats.

Rats exposed to acute unavoidable stress develop a deficit in escaping avoidable aversive stimuli that lasts as long as unavoidable stress exposure is repeated. A 3-week exposure to unavoidable stress also reduces dopamine (DA) output in the nucleus accumbens shell (NAcS). This study showed that a 7-day exposure to unavoidable stress induced in rats an escape deficit and a decrease in extraneuronal DA basal concentration in the NAcS. Moreover, animals had reduced DA and serotonin (5-HT) accumulation after cocaine administration in the medial pre-frontal cortex (mPFC) and NAcS, compared with control animals. After a 3-week exposure to unavoidable stress, escape deficit and reduced DA output in the NAcS were still significant at day 14 after the last stress administration. In the mPFC we observed: (i) a short-term reduction in DA basal levels that was back to control values at day 14; (ii) a decrease in DA accumulation at day 3 followed by a significant increase beyond control values at day 14; (iii) a significant reduction in 5-HT extraneuronal basal levels at day 3, but not at day 14. Finally, a significant decrease in 5-HT accumulation following cocaine administration was present in the NAcS and mPFC at day 3, but not at day 14. In conclusion, a long-term stress exposure induced long-lasting behavioral sequelae associated with reproducible neurochemical modifications.

The meaning of dreams in the psychotic state. Theoretical considerations and clinical applications.

The authors consider that the Freudian theory of dreams is not directly applicable to psychotic and borderline patients with their constantly varying states of mental integration. Because these patients' dreams lack associations, the usual psychoanalytic approach cannot be used to ascertain their meaning. After reviewing the literature on the specific quality of dreams in the psychotic state, the authors point out that such dreams have nothing to do with the metaphorical language of the dream work but instead express the concreteness of the hallucinatory construction. For this reason, a dream's meaning may fail to be understood by the patient even if it seems clear to an observer. Yet the analyst's reception of a 'psychotic dream' is a unique and essential source of valuable information on the manner of construction of the delusional system, allowing analytic work on the psychotic nucleus. In the authors' view, such dreams may help the analyst and the patient--while still lucid--to acquire insight, thus affording a stable foundation for emergence from psychosis. The paper includes some case histories, in one of which a psychotic female patient is enabled by work on dreams to reconstruct a psychotic episode and thereby to ward off an imminent fresh lapse into psychosis.

A study of the antidepressant activity of Hypericum perforatum on animal models.

The treatment of non-selected depressed patients with a hydro-alcoholic extract of Hypericum perforatum has been reported to have an efficacy similar to that of classical antidepressants. The effects of H. perforatum on three animal depression models have been studied: (a) an acute form of escape deficit (ED) induced by unavoidable stress; (b) a chronic model of ED, which can be maintained by the administration of mild stressors on alternate days; (c) a model of anhedonia based on the finding that repeated stressors prevent the development of appetitive behavior induced by vanilla sugar in satiated rats fed ad libitum. H. perforatum: (i) acutely protects animals from the sequelae of unavoidable stress; (ii) reverts the chronic escape deficit state maintained by repeated stressors and (iii) preserves the animal's capacity to acquire motivated appetitive behavior. Exposure to chronic stress not only induces escape deficit, but also decreases extraneuronal levels of dopamine in the nucleus accumbens shell; both behavioral and neurochemical effects are reverted by long-term treatment with antidepressants. Three-week treatment with H. perforatum reverted the chronic stress effect on extraneuronal dopamine in the nucleus accumbens. A consistent body of data in the literature suggests that, among the components of H. perforatum extract, hyperforin is the compound (or one of the compounds) responsible for the antidepressant activity. We compared the efficacy of the total extract with the efficacy of hyperforin after p.o. administration. In the acute-escape deficit model, hyperforin showed a potency of about ten times that of the total extract in protecting rats from the sequelae of unavoidable stress. Thus, hyperforin appears to be the most likely active component responsible for the antidepressant activity of H. perforatum.