Modification of mRNA by methylation is involved in post-transcriptional regulation of gene expression by affecting the splicing, transport, stability and translation of mRNA. Methylation of adenosine at N6 (m6A) is one of the most common and important cellular modification occurring in the mRNA of eukaryotes. Evidence that m6A mRNA methylation is involved in regulation of stress response and that its dysregulation may contribute to the pathogenesis of neuropsychiatric disorders is accumulating. We have examined the acute and subchronic (up to 18 days once per day intraperitoneally) effect of the first METTL3/METTL14 activator compound CHMA1004 (methyl-piperazine-2-carboxylate) at two doses (1 and 5 mg/kg) in male and female rats. CHMA1004 had a locomotor activating and anxiolytic-like profile in open field and elevated zero-maze tests. In female rats sucrose consumption and swimming in Porsolt’s test were increased. Nevertheless, CHMA1004 did not exhibit strong psychostimulant-like properties: CHMA1004 had no effect on 50-kHz ultrasonic vocalizations except that it reduced the baseline difference between male and female animals, and acute drug treatment had no effect on extracellular dopamine levels in striatum. Subchronic CHMA1004 altered ex vivo catecholamine levels in several brain regions. RNA sequencing of female rat striata after subchronic CHMA1004 treatment revealed changes in the expression of a number of genes linked to dopamine neuron viability, neurodegeneration, depression, anxiety and stress response. Conclusively, the first-in-class METTL3/METTL14 activator compound CHMA1004 increased locomotor activity and elicited anxiolytic-like effects after systemic administration, demonstrating that pharmacological activation of RNA m6A methylation has potential for neuropsychiatric drug development.

Microplastics (MPs) pollution has been a hot research topic in recent years. MPs are ubiquitous throughout the ecological environment and are eventually accumulated in organisms through inhalation or ingestion. However, given that MPs are inert pollutants, their effects on organisms are not clear. In previous study, we have investigated the effects of polyethylene terephthalate MPs on physiology of Drosophila. What is the effect of polypropylene microplastics (PP-MPs)? The results of our experiments show that being exposed to high concentration of PP-MPs have significant effect on Drosophila. PP-MPs exposure can significantly increase locomotor activity and shorten the time of group sleep in Drosophila. In the presence of high concentrations of PP-MPs, the triglyceride content was reduced in females and their ability of egg production was affected. However, there was no significant effect on the level of protein and carbohydrate, or on the food intake. Our experimental results can provide some preliminary data for assessing the potential hazard of PP-MPs to other organisms.

Noncompetitive N-methyl-d-aspartate receptor (NMDAr) antagonists can elicit many of the symptoms observed in schizophrenia in healthy humans, and induce a behavioural phenotype in animals relevant to psychosis. These compounds also elevate the power and synchrony of gamma (γ) frequency (30–80 Hz) neural oscillations. Acute doses of antipsychotic medications have been shown to reduce ongoing γ power and to inhibit NMDAr antagonist-mediated psychosis-like behaviour in rodents. This study aimed to investigate how a chronic antipsychotic dosing regimen affects ongoing cortical γ oscillations, and the electrophysiological and behavioural responses induced by the NMDAr antagonist ketamine. Male Wistar rats were chronically treated with haloperidol (0.25 mg/kg/d), clozapine (5 mg/kg/d), LY379268 (0.3 mg/kg/d) or vehicle for 28 d, delivered by subcutaneous (s.c.) osmotic pumps. Weekly electrocorticogram (ECoG) recordings were acquired. On day 26, ketamine (5 mg/kg, s.c.) was administered, and ECoG and locomotor activity were simultaneously measured. These results were compared with data generated previously following acute treatment with these antipsychotics. Sustained and significant decreases in ongoing γ power were observed during chronic administration of haloperidol (64%) or clozapine (43%), but not of LY379268 (2% increase), compared with vehicle. Acute ketamine injection concurrently increased γ power and locomotor activity in vehicle-treated rats, and these effects were attenuated in rats chronically treated with all three antipsychotics. The ability of haloperidol or clozapine to inhibit ketamine-induced elevation in γ power was not observed following acute administration of these drugs. These results indicate that modulation of γ power may be a useful biomarker of chronic antipsychotic efficacy.

At the onset of sexual maturation, European eels Anguilla anguilla exhibit high locomotor activity which may correspond to migratory restlessness. We measured activity of captive eels and determined whether it correlated with downstream runs of silver eels as well as changes in environmental factors. Groups of eels at different stages of the silvering process (yellow to silver stage) were tagged and placed in separate tanks supplied with either river or tap water. Activity was measured by means of a flat-board antenna placed vertically in the middle of the tank at the surface of the water. Wild migrating silver eels were caught in the nearby river. Activity of eels in the river water tanks increased 1 to 2 days before downstream migrating eels were caught in the trap, and concurrently with a rise in turbidity and a decrease in conductivity. Activity of eels in the tap water tank showed a different pattern, which did not correspond to downstream runs. A peak in activity corresponded to a drop in tap water pH. It is concluded that eels do show periods of high locomotor activity at the onset of migration and this could be used to predict downstream migration. Movements are triggered by changes in water composition (as opposed to changes in discharge, atmospheric pressure and lunar cycle) measured using turbidity and/or conductivity as proxies. If eels are able to detect such small changes in water conductivity (80 µS cm−1), they may use it to find their way to the estuary.

The non-competitive NMDA receptor antagonist MK-801 elicits a behavioural syndrome in rodents characterized by hyperlocomotion and stereotypies, which is antagonized by antipsychotic drugs. NMDA receptor antagonists increase prefrontal cortex (PFC) activity in rodents, as assessed by electrophysiological and neurochemical measures. The increase in glutamate outflow induced by systemic MK-801 administration in the medial PFC (mPFC) is prevented by the local administration of clozapine (Clz). In the present study, we examine whether a PFC lesion alters the behavioural syndrome induced by MK-801 in rats and the Clz-induced antagonism of MK-801 actions. We evaluated the hyperlocomotion, stereotypies and other behavioural changes induced by MK-801 in the open field and the effect of electrolytic lesions of the mPFC, and of cortical transection on the behavioural syndrome induced by MK-801 and its reversal by Clz. MK-801 (0.1–0.2 mg/kg i.p.) reduced rearings but only the higher dose induced hyperlocomotion. At this dose, MK-801 also increased disorganized movements, head weavings, and induced ataxia signs. An electrolytic lesion of the mPFC markedly reduced the number of rearings pre-treatment but caused a very slight attenuation of MK-801-induced hyperlocomotion. Cortical transection did not significantly alter MK-801 effects. Clz administration (1 mg/kg s.c.) significantly attenuated hyperlocomotion, head weavings and ataxia signs induced by MK-801 but did not prevent the decrease in rearings. The effect of Clz was essentially unaffected by electrolytic lesions of the mPFC. These results show that MK-801-induced motor syndrome and its reversal by Clz are mostly independent on PFC integrity.

The behavioural response of the sleepy lizard Tiliqua rugosa to an extended drought was examined in spring and summer 2002. Observations of the behaviour and use of microhabitat by radio-tagged lizards for spring in 2000–2002 showed that the lizards in 2002 suffered decreased body mass and increased mortality, were less active, showed reduced mating behaviour and increased use of burrows when compared with the more normal wetter years of 2000 and 2001. The lizards lost significant mass owing to dehydration and starvation. An ‘onboard’ data logger recorded lizard stride frequency and body temperature continuously for 4 months on 11 lizards during the drought of 2002. The normally diurnal heliothermic sleepy lizards responded to rare rainfall events during the drought whenever they occurred, day or night, by emerging from burrows or other shelters for extended periods of activity with sub-optimal body temperatures as low as 8.5 °C. They moved more often, and with higher stride frequencies during periods of rain than during dry periods, both overnight and during the day. As a consequence of this extended activity under physiological stress, the lizards were able to respond to naturally occurring transient opportunities for food and water that would not have been available if they were only active at optimal body temperatures. In an area where freestanding water is rarely available, the lizards were able to access limited water by licking substrate. They also gained water and perhaps nutrition by consuming the temporarily rehydrated thalli of the free-living terrestrial cyanobacterium Nostoc commune. Such behaviour enabled lizards to regain much of the mass lost before the rainfall and probably enabled many lizards to survive until more normal food sources became available. These rare events may have a significant effect on the shaping of the sleepy lizards phenotypic capacities outside routine day-to-day activities.