Venlafaxine is an antidepressant and anti-anxiety drug that has been detected in municipal wastewater at low μg/L concentrations. In this study, the nest-defense behavior of adult male fathead minnows (Pimephales promelas) was observed in fish exposed for a full lifecycle to venlafaxine nominal concentrations of 0.88, 8.8, and 88 μg/L (i.e. 1, 9.3, 75 μg/L mean measured concentrations). Nest-defense behaviors quantified were the time taken to contact a dummy intruder fish (on a flexible stick, held near each nest) and the number of contacts made during a 1 min period. In male fathead minnows exposed to venlafaxine over a full lifecycle at environmentally relevant nominal concentrations (i.e. 0.88 and 8.8 μg/L) no significant effects were observed in behavior. However, in males exposed over a full lifecycle to the highest concentration of venlafaxine (i.e. 88 μg/L), nest-defense behaviors were increased in males with empty nests, as shown by the significantly elevated percentage of empty-nest males that made contact with the dummy intruder fish (89%) relative to the lower percentage of contacts (65%) among the Control males (p = 0.046). Lifecycle exposure to high venlafaxine (88 μg/L) caused males to over-protect their empty nests. Environmental venlafaxine concentrations are approximately 70 x lower than this, so it is unlikely that behavioral changes from venlafaxine exposure would occur in the environment. Normal nest defense behaviours in control males varied, depending on whether they were protecting empty nests or nests with eggs. Compared to Control males with empty nests, more Control males with eggs in their nests made contact with the dummy intruder fish (p = 0.014), contact was faster (i.e. <10 s, p = 0.011), and they hit the dummy intruder fish more times in 1 min (p = 0.031) This study is the first to assess reproductive behaviors in fish exposed to an antidepressant over a full lifecycle.

This study was carried out to provide baseline information on the concentrations of pharmaceuticals in Kuwait's coastal waters. Samples were collected over four sampling campaigns from various outfalls that occasionally discharged water into the marine environment and analyzed for a range of pharmaceuticals including analgesic/anti-inflammatories, antibiotics, anticoagulant, antidiabetic, antihelmintics, antihypertensives, antiplatelet agent, asthma medication, β-blocking agent, calcium channel blocker, diuretic, histamine H1 and H2 receptor antagonist, lipid regulators/cholesterol-lowering, prostatic hyperplasia, psychiatric drug, sedation and muscle relaxant, synthetic glucocorticoid, tranquilizer and x-ray contrast media. The levels varied between the detection limits of the method and a maximum of 28,183 ng/L for analgesics/anti-inflammatories. The highest pharmaceutical concentrations were in samples collected during the September campaign, possibly linked to the increased prescription of these medications to treat infectious diseases and flu prevalent in Kuwait during the winter months. The spatial variation is concentration is evident with KISR site being most polluted as hospital wastewater is discharged at the site. This study provides the first dataset on the concentrations of pharmaceuticals in the seawater in Kuwait and possibly the wider Arabian Gulf. Kuwait's coastal water pharmaceutical concentrations derived from this study exceed those reported from the Spanish coast, the Hong Kong harbour, the Bohai and the Yellow seas. More studies are needed to evaluate the environmental impact that these residues may have on non-target organisms.

Genistein is a phytoestrogen, which is structurally similar to 17β-estradiol. It is present in plants, food, and as a contaminant in effluents. In this article, we demonstrate the effects of embryonic exposure to three different concentrations of genistein (10 μg/L, 40 μg/L, and 80 μg/L) which is similar to those found in effluents. Zebrafish eggs were exposed during the first 72 h post-fertilization (hpf). Heart rate was evaluated at 48 hpf and mortality rate was assessed during the first 72 hpf. The light/dark (LDT) and open field (OFT) behavioral tests were applied to the larvae (6 dpf), and the novel tank (NTT), social preference (SPT), light-dark (LDT), and sexing tests were performed on adult fish (90 dpf). Embryonic exposure to genistein caused anxiolytic-like behavior in both larvae and adult animals. In adult stage, we observed an increase in locomotor activity and antisocial behavior in the concentration of 40 μg/L. There was an increase in the mortality rate in all concentrations when compared to the control and an increase in heart rate at the concentration of 80 μg/L. Exposure to 10 μg/L generated a higher frequency of females when compared to the control group. Our results show that exposure to genistein during the embryonic phase brings damage in the short and long term as it increases the mortality rate and leads to behavioral disorders both in the larval stage, with perpetuation until adult stage. The anxiolytic-like effect and less social interaction are effects that harm fish survival.

Psychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L⁻¹ to 10 mg L⁻¹. Lethal concentrations 50 % (LC₅₀) were estimated at 840, 841 and 9,136 μg L⁻¹ for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L⁻¹ for citalopram and oxazepam, 12.2 μg L⁻¹ for cyamemazine, 100 μg L⁻¹ for fluoxetine, 1,000 μg L⁻¹ for sertraline and >10,000 μg L⁻¹ for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations.

The increase use of pharmaceutical compounds in veterinary practice and human population results in the ubiquitous presence of these compounds in aquatic ecosystems. Because pharmaceuticals are highly bioactive, there is concern about their toxicological effects in aquatic organisms. Therefore, the aim of this study was to assess the effects of an effluent from a psychiatric hospital (containing a complex mixture of 25 pharmaceutical compounds from eleven therapeutic classes) on the freshwater clam Corbicula fluminea using a proteomic approach. The exposure of C. fluminea to this complex effluent containing anxiolytics, analgesics, lipid regulators, beta blockers, antidepressants, antiepileptics, antihistamines, antihypertensives, antiplatelets and antiarrhythmics induced protein changes after 1 day of exposure in clam gills and digestive gland more evident in the digestive gland. These changes included increase in the abundance of proteins associated with structural (actin and tubulin), cellular functions (calreticulin, proliferating cell nuclear antigen (PCNA), T complex protein 1 (TCP1)) and metabolism (aldehyde dehydrogenase (ALDH), alcohol dehydrogenase, 6 phosphogluconate dehydrogenase). Results from this study indicate that calreticulin, PCNA, ALDH and alcohol dehydrogenase in the digestive gland and T complex protein 1 (TCP1)) and 6 phosphogluconate dehydrogenase in the gills represent useful biomarkers for the ecotoxicological characterization of psychiatric hospital effluents in this species.

The present study was conducted to evaluate the effect of Cochlospermum religiosum (CSR) in animal models of depression and anxiety. The CSR leaves are well known for their sedative, antibacterial, antifungal antioxidant, memory enhancing, anxiolytic and antidepressant potential. In present study, the extract of the leaves is used to relieve the anxiolytic and antidepressant potential. The leaves of CSR were investigated for antidepressant and anxiolytic activities in mice behavioural models namely, spontaneous locomotor activity (SLA), forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM) and marble burying behaviour (MBB). The mechanism was supported by reserpine-induced hypothermia (RIH). Further, the in vivo synergistic evaluation of the CSR leaf extract was evaluated with imipramine and fluoxetine. The treatment of mice with ethanolic extract of CSR leaves for 7 days resulted significant antidepressant and anxiolytic effects (p < 0.05 for 50 mg/Kg p.o / p < 0.01 for 100 mg/kg p.o) with null impact on baseline locomotor activity. Further, the study on rat RIH model revealed that the CSR (50 mg/kg p.o) predominantly antagonized the effect (p < 0.05) of reserpine. Furthermore, synergic action was screened by co-administration of leaf extracts of CSR with fluoxetine (10 mg/Kg, i.p.) and imipramine (10 mg/Kg, i.p.) at below therapeutic dose levels using FST, TST, EPM and MBB. The synergistic effect was significant (p < 0.05) for both antidepressant and anxiolytic activities as compared to therapeutic doses of extract, imipramine and fluoxetine.

The increasing presence of pharmaceutical products in municipality wastewaters has raised serious environmental concerns. Ozonation is one of the advanced oxidation processes that can degrade these substances, instead of simply transferring them from aqueous to another phase. Treatability studies applying ozonation to degrade benzodiazepine drugs are scarce. The aim of this investigation was to apply design of experiments (DoE) to optimize ozonation processes for removal of bromazepam, clonazepam, and diazepam from two effluents of municipal wastewater treatment plants (WWTP1 and WWTP2) both located in Rio de Janeiro City, Brazil. During a preliminary study using ultrapure water, OHº radicals were more efficient (removal efficiency greater than 99% (< LOQ) at pH = 10, 15 min) than O₃ in degrading all psychoactive drugs (removal efficiency from 46 to 85% at pH = 4, 15 min). The optimum values for the tested variables were pH = 8.03; O₃ specific dose = 4.8 mgO₃.mgDOC⁻¹; and O₃ mass flow rate = 22.07 mgO₃.min⁻¹. The WWTP1 and WWTP2 effluents were treated under optimized conditions by ozonation in two effluent volumes (5L and 8L). When 8 L effluent was treated, the degradation of all benzodiazepine drugs was improved, due to the higher water column used, which favors the mass transfer of O₃ from the gas phase to the liquid phase, promoting greater contact between oxidant and target compounds. Using a specific dose of 1.8 mgO₃.mgDOC⁻¹, more than 93% of all anxiolytic drugs were removed from 8 L of WWTP2 effluent, whereas for the WWTP1, more than 90% were removed using 2.7 times higher specific dose (4.8 mgO₃.mgDOC⁻¹).

Despite a growing scientific attention on ecological impact of emerging pollutants (EPs) such as pharmaceuticals, personal care products, and pesticides, knowledge gaps remain regarding mixture toxicity and effects on aquatic organisms. Several EPs were screened in seawater (Normandy, France), and the ecotoxicity of five compounds, chosen on their occurrence in ecosystems and use worldwide, was assessed and were the biocides methylparaben (MP) and triclosan (TCS), a pesticide degradation product (AMPA), and the pharmaceuticals venlafaxine (VEN) and carbamazepine (CBZ). The acute or sub-chronic toxicity, alone or in binary/ternary mixtures of three of them (CBZ, AMPA, and MP), was assessed on one marine and two freshwater organisms: Crassostrea gigas, Pseudokirchneriella subcapitata, and Daphnia magna. TCS and AMPA were, respectively, the most (EC₅₀ < 1 mg L⁻¹) and the least (EC₅₀ > 50 mg L⁻¹) toxic chemicals for the four endpoints (algal growth inhibition, daphnia immobilization, oyster embryotoxicity, and metamorphosis). The anxiolytic VEN (EC₅₀ < 1 mg L⁻¹) was particularly toxic to oyster larvae showing sensitivity difference between freshwater and marine organisms. If all the mixtures appeared to be in the same range of toxicity, the joint-toxic effects mainly led to synergistic or antagonistic interactions compared to single-compound toxicity. The data also highlighted species-dependent differing models of toxicity and underscored the need for an awareness of cocktail effects for better ecological risk assessment.

Although the efficiency of haloxyfop-p-methyl ester (HPME) as selective herbicide is acknowledged, its impact on non-target organisms is poorly known. It is not known whether the short exposure of mammals to low HPME concentrations (consistent with a realistic contamination scenario) poses risks to these animals. Thus, the aim of the current study is to evaluate the effects of HPME on the anti-predatory behavior of female Swiss mice exposed to it. The animals were divided in groups: non-exposed (control) and exposed (route: i.p., for 2 days) to different herbicide concentrations (2.7 × 10⁻⁴ g/kg and 2.7 × 10⁻² g/kg of body weight), which were considered environmentally relevant predicted concentrations. The animals were subjected to the open field and elevated plus-maze tests; results showed that the HPME did not lead to anxiolytic or anxiety behavior, or to locomotive changes in the tested animals, fact that was confirmed through the Basso Mouse Scale for locomotion scores. On the other hand, animals exposed to the herbicide were incapable of recognizing the snake as potential predator. Animals in the control group, exposed to a real snake (Pantherophis guttatus) remained longer in the safety zone of the test device, presented lower frequency of self-grooming behaviors for a shorter period-of-time, besides showing longer freezing time, which was not observed in animals exposed to HPME. Therefore, our study indicates the ecotoxicological potential of the herbicide, since anti-predatory behavior disorders may affect preys’ responses and population dynamics.

The synthetic estrogen, 17-α-ethinylestradiol (EE2), present in contraceptive pills, is an endocrine-disrupting chemical (EDC) that can be found in the aquatic environment. We examined the impacts of EE2 on zebrafish behavioral and physiological responses through the novel tank test (NTT), which measures anxiety-like behavior; the mirror-induced aggression (MIA) test, which measures aggressiveness; and the social preference test (SPT), which measures social cohesion. The steroid hormone levels were also measured. Here, we show that exposure to EE2 impairs stress responses by regulating the levels of specific hormones and eliciting an anxiolytic response, increasing aggression, and reducing social preference in zebrafish. In nature, these changes in behavior compromise reproduction and anti-predator behaviors, which, in turn, affects species survival. The maintenance of an intact behavioral repertoire in zebrafish is essential for their survival. Thus, our results point to the danger of environmental contamination with EE2 as it may alter the dynamics of the prey–predator relationship.