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Acetaminophen (AAP; also known as paracetamol) is the most used and only recommended analgesic and antipyretic among pregnant women and young children. However, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and adverse neurobehavioral effects later in life. We hypothesized that the cannabinoid receptor type 1 (CB1R) may be involved in the developmental neurotoxicity of AAP, owing to its interaction with the endocannabinoid system. Here we test if CB1R agonist WIN 55 212-2 (WIN) and AAP can interact when exposure occurs during a neurodevelopmental stage known for increased growth rate and for its vulnerability to AAP exposure. We exposed male NMRI mice on postnatal day 10 to different combinations of AAP and WIN. Adult mice, neonatally co-exposed to AAP and WIN, displayed a significant lack of habituation in the spontaneous behavior test, when compared with controls and single agent exposed mice. These adult adverse effects may at least in part be explained by a reduction of transcript levels of hippocampal synaptophysin (Syp) and tropomyosin receptor kinase B (Trkb), and cerebral cortical fatty acid amide hydroxylase (Faah), 24h after exposure. These findings are consistent with our hypothesis that AAP and WIN can interact when exposure occurs during early postnatal brain development in mice. Assuming our results are relevant for humans, they raise concerns on AAP safety because it is the only recommended analgesic and antipyretic during pregnancy and early life.

The CNS of breast feeding infants and toddlers may be exposed to persistent organic pollutants via lactational transfer. Here, 10 days old mice were exposed to single oral doses of either PFOS, PBDE99 or vehicle control and were examined for changes in dopaminergic gene transcription in CNS tissue collected at 24 h or 2 months post exposure.qPCR analyses of brain tissue from mice euthanized 24 h post exposure revealed that PFOS affected transcription of Dopamine receptor-D5 (DRD5) in cerebral cortex and Tyrosine hydroxylase (TH) in the hippocampus. At 2 months of age, mice neonatally exposed to PFOS displayed decreased transcription of Dopamine receptor-D2 (DRD2) and TH in hippocampus. No significant changes in any of the tested genes were observed in PBDE99 exposed mice. This indicates that PFOS, but not PBDE99, affects the developing cerebral dopaminergic system at gene transcriptional level in cortex and hippocampus, which may account for some of the mechanistic effects behind the aetiology of neuropsychiatric disorders.

Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents and surface waters around the world. Citalopram and other selective serotonin re-uptake inhibitors have, at concentrations that occur in nature, been shown to have behavioural as well as physiological effects on fish and other animals. This study is the result of several different experiments, intended to analyse different aspects of behavioural effects of chronic citalopram exposure in fish. Our model species the three-spine stickleback is common in the entire northern hemisphere and is considered to be a good environmental sentinel species. Female three-spine sticklebacks were exposed to 0, 1.5 and 15 μg/l nominal concentrations of citalopram for 21 days and subjected to the novel tank (NT) diving test. In the NT test, the fish exposed to 1.5 μg/l, but not the 15 μg/l fish made a significantly higher number of transitions to the upper half and stayed there for significantly longer time than the fish exposed to 0 μg/l. The 15 μg/l group, however, displayed a significantly lower number of freeze bouts and a shorter total freezing time. The test for locomotor activity included in the NT test showed that fish treated with 1.5 and 15 μg/l displayed a significantly higher swimming activity than control fish both 5–7 and 15–17 minutes after the start of the experiment. In the next experiment we compared fish exposed to 1.5 μg/l and 0.15 μg/l to pure water controls with regard to shoaling intensity and found no effect of treatment. In the final experiment the propensity of fish treated with 1.5 μg/l to approach an unknown object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically significant effects. It is concluded that citalopram changes the behaviour of the three-spine stickleback in a way that is likely to have ecological consequences and that it must not be considered an environmentally safe pharmaceutical.

Exposure to estrogenic endocrine disruptors (EDCs) during development affects fertility, reproductive and non-reproductive behavior in mammals and fish. These effects can also be transferred to coming generations. In fish, the effects of developmental EDC exposure on non-reproductive behavior are less well studied. Here, we analyze the effects of 17α-ethinylestradiol (EE₂) on anxiety, shoaling behavior and fertility in zebrafish after developmental treatment and remediation in clean water until adulthood. Zebrafish embryos were exposed from day 1 to day 80 post fertilization to actual concentrations of 1.2 and 1.6 ng/L EE₂. After remediation for 82 days non-reproductive behavior and fertilization success were analyzed in both sexes. Males and females from the 1.2 ng/L group, as well as control males and females, were bred, and behavior of the untreated F1 offspring was tested as adults.

Developmental treatment with 1.2 and 1.6 ng/L EE₂ significantly increased anxiety in the novel tank test and increased shoaling intensity in both sexes. Fertilization success was significantly reduced by EE₂ in both sexes when mated with untreated fish of opposite sex. Progeny of fish treated with 1.2 ng/L EE₂ showed increased anxiety in the novel tank test and increased light avoidance in the scototaxis test compared to control offspring.

In conclusion, developmental exposure of zebrafish to low doses of EE₂ resulted in persistent changes in behavior and fertility. The behavior of unexposed progeny was affected by their parents' exposure, which might suggest transgenerational effects.

Maternally and lactionally transferred persistent organic pollutants may interfere with CNS development. Here, 10-day-old male mice were exposed to single oral doses of PFOS (perflourooctanosulphonate) or PBDE 99 (2,2',4,4',5-penta-bromodiphenyl ether), and examined for changes in cholinergic gene transcription in the CNS 24 h and 7 weeks later. 24 h after exposure qPCR analyses revealed decreased transcription of nAChR-beta 2 and AChE in cortex, and increased mAChR-5 in hippocampus of PFOS treated mice. Neonatal PFOS treatment altered spontaneous behaviour at 2 months of age but did not affect gene transcription in adults. At 2 months of age neonatally PBDE 99 treated mice had altered spontaneous behaviour, and cortical transcription of AChE, nAChR-alpha 4, nAChR-beta 2 and mAChR-5 were elevated. Our results indicate that PFOS and PBDE 99 affects the developing central cholinergic system by altering gene transcription in cortex and hippocampus, which may in part account for mechanisms causing changes in spontaneous behaviour.

Environmental contaminants can cause alterations that can be transgenerationally transmitted to subsequent generations. Estrogens are among those contaminants shown to induce heritable changes that persist over generations in mammals. Results in other vertebrates are few. We have analyzed the effects on anxiety of 17 alpha-ethinyl estradiol (EE2) in the F1 and F2 generations in guppies, Poecilia reticulate, obtained from F0 fish maternally exposed to 0 or 20 ng/L EE2 until birth. F0 males and females were bred with fish of the same treatment but different families producing F1 offspring. Behavior in the novel tank test at 6 months revealed that males with EE2-exposed parents had significantly longer latency to the upper half of the tank than control males, while no EE2 effects were observed in females. Also in F2, obtained from F1 as above, males in the EE2 group had longer latency time compared to control males, with no differences due to EE2-exposure of F0 observed in females. In the scototaxis (light/dark preference) test, latency to first transition to black compartment and total transitions to black were significantly altered in females due to EE2 exposure of F0 while the total time in black was higher in males with EE2-exposed F0 compared with controls. The increased anxiety in the F2 generation demonstrates a transgenerational anxiety phenotype and shows that non-reproductive behavior can be transgenerationally modified by estrogens in fish.

There are several different types of pesticides globally used, all with their own characteristics and toxicological potency. In the present study we have exposed male mice neonatally to different doses of four different types of pesticides, carbaryl (carbamate) chlorpyrifos (organophosphate), cypermethrin (pyrethroid) and endosulfan (organochlorine), and tested them for spontaneous behavior in a novel home environment at adult age. The doses used were 0.5 – 20 mg carbaryl/kg bw, 0.1 – 5.0 mg chlorpyrifos/kg bw, 0.1 – 5.0 mg cypermethrin/kg bw and 0.05 – 20 mg endosulfan/kg bw. All four pesticides induced adult disturbances in the spontaneous behavior in a novel home environment, affecting cognitive function, at 2 months of age. Carbaryl induced a dose-response related effect on spontaneous behavior from 5 mg/kg bw and up, while chlorpyrifos only induced a weak effect with the highest dose tested (5 mg/kg bw). The pyrethroid cypermethrin induced dose-response related neurotoxicity from 0.5 mg/kg bw and up. The organochlorine endosulfan also induced dose-response related neurotoxicity from 0.1 mg/kg bw and up These disturbances also persisted when the animals were re-observed at 4 months of age, indicating that these effects are long-lasting or even irreversible. From this study we conclude that endosulfan seem to be the most potent, of these four compounds, to induce cognitive behavioral effects in the adult after neonatal exposure, while carbaryl has the lowest potency to induce these types of neurotoxic effects.