Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either i.p. saline, mephedrone (10mg/kg), caffeine (10mg/kg) or combined caffeine and mephedrone twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day two), elevated plus maze (EPM, day eight) exploration, rectal temperature changes (day nine) and prepulse inhibition of acoustic startle (PPI, day 15) response were assessed. Seven days after the final injection, brain regions were collected for measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

The psychoactive effects of mephedrone are commonly compared to those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action users often employ repeated administration to maintain its psychoactive actions. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels, and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1ml/kg, i.p.) or mephedrone HCl (10mg/kg) at 2h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (5,7-DHT, 150μg) or 6-hydroxydopamine (6-OHDA, 300μg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30min) with the 5-HT1A receptor antagonist WAY-100635 (0.5mg/kg), 5-HT1B receptor antagonist GR 127935 (3mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing), and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors

Is the Insect Apocalypse upon us? How to Find Out

In recent decades, entomologists have documented alarming declines in occurrence, taxonomic richness, and geographic range of insects around the world. Additionally, some recent studies have reported that insect abundance and biomass, often of common species, are rapidly declining, which has led some to dub the phenomenon an “Insect Apocalypse”. Recent reports are sufficiently robust to justify immediate actions to protect insect biodiversity worldwide. We caution, however, that we do not yet have the data to assess large-scale spatial patterns in the severity of insect trends. Most documented collapses are from geographically restricted studies and, alone, do not allow us to draw conclusions about insect declines on continental or global scales, especially with regards to future projections of total insect biomass, abundance, and extinction. There are many challenges to understanding insect declines: only a small fraction of insect species have had any substantial population monitoring, millions of species remain unstudied, and most of the long-term population data for insects come from human-dominated landscapes in western and northern Europe. But there are still concrete steps we can take to improve our understanding of potential declines. Here, we review the challenges scientists face in documenting insect population and diversity trends, including communicating their findings, and recommend research approaches needed to address these challenges

The long-term population dynamics of common wasps in their native and invaded range

Summary 1. Populations of introduced species are often thought to perform differently, or experience different population dynamics, in their introduced range compared to their native habitat. Differences between habitats in climate, competition or natural enemies may result in populations with varying density dependence and population dynamics. 2. We examined the long‐term population dynamics of the invasive common wasp, Vespula vulgaris, in its native range in England and its invaded range in New Zealand. We used 39 years of wasp density data from four sites in England, and 23 years of data from six sites in New Zealand. Wasp population time series was examined using partial rate correlation functions. Gompertz population models and multivariate autoregressive state‐space (MARSS) models were fitted, incorporating climatic variation. 3. Gompertz models successfully explained 59–66% of the variation in wasp abundance between years. Density dependence in wasp populations appeared to act similarly in both the native and invaded range, with wasp abundance in the previous year as the most important variable in predicting intrinsic rate of increase (r). No evidence of cyclic population dynamics was observed. 4. Both the Gompertz and MARSS models highlighted the role of weather conditions in each country as significant predictors of annual wasp abundance. The temporal evolution of wasp populations at all sites was best modelled jointly using a single latent dynamic factor for local trends, with the inclusion of a latent spring weather covariate. That same parsimonious multivariate model structure was optimal in both the native and invaded range. 5. Density dependence is overwhelmingly important in predicting wasp densities and ‘wasp years’ in both the native and invaded range. Spring weather conditions in both countries have a major influence, probably through their impact on wasp colony initiation and early development. The population dynamics in the native range and invaded range show no evidence of cyclic boom‐and‐bust dynamics. Invasive species may not exhibit different population dynamics despite considerable variation in abundances throughout their distribution

Key actors in driving behavioural change in relation to on-farm biosecurity; a Northern Ireland perspective

Background: Agriculture and farming are valued contributors to local economy in Northern Ireland (NI). There is limited knowledge about farmers’ behaviours and attitudes towards disease biosecurity measures. As part of a larger project, a scenario-based workshop with key stakeholders was organised by the Agri-Food and Biosciences Institute (AFBI)-NI in December 2015. Results: A total of 22 participants belonging to 12 different institutions took part in the workshop. Participants were presented with an overview of previously conducted biosecurity research in NI and England. In small groups, participants were subsequently asked to discuss and give their opinions about a series of questions across four key areas in a semi-structured approach with an external facilitator. The key areas were 1- disease risk perception at the farm level; 2-perceived barriers to implementing on farm biosecurity measures; 3- avenues to successful behaviour change and 4-key industry responsibilities and roles. The discussion showed that training in biosecurity for farmers is important and necessary. Training was recommended to be provided by veterinary surgeons, preferably via a face-to-face format. The discussion addressing disease disclosure proved particularly challenging between those who were prospective buyers of cattle, and those who sold cattle. Conclusions: This workshop provided a unique and invaluable insight into key issues regarding farm level biosecurity activities. From a policy perspective, delivering improved on-farm biosecurity must be addressed via a multidisciplinary approach. This can only be achieved with active involvement, commitment and support of a number of key industry and government stakeholders

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Long-term changes in the abundance of flying insects

For the first time, long-term changes in total aerial insect biomass have been estimated for a wide area of Southern Britain. Various indices of biomass were created for standardised samples from four of the Rothamsted Insect Survey 12.2 m tall suction traps for the 30 years from 1973 to 2002. There was a significant decline in total biomass at Hereford but not at three other sites: Rothamsted, Starcross and Wye. For the Hereford samples, many insects were identified at least to order level, some to family or species level. These samples were then used to investigate the taxa involved in the decline in biomass at Hereford. The Hereford samples were dominated by large Diptera, particularly Dilophus febrilis, which showed a significant decline in abundance. Changes in agricultural practice that could have contributed to the observed declines are discussed, as are potential implications for farmland birds, with suggestions for further work to investigate both cause and effect

Calbindin Deficits May Underlie Dissociable Effects of 5-HT6 and mGlu7 Antagonists on Glutamate and Cognition in a Dual-Hit Neurodevelopmental Model for Schizophrenia

© 2020, The Author(s). Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates “dual-hit” neurodevelopmental insults like neonatal phencyclidine plus isolation rearing (PCP-Iso). Glutamatergic dysfunction contributes to schizophrenia pathophysiology and may represent a treatment target, so we used enzyme-based microsensors to evaluate basal- and drug-evoked glutamate release in hippocampal slices from rats that received neonatal PCP and/or isolation rearing. 5-HT6 antagonist-evoked glutamate release (thought to be mediated indirectly via GABAergic disinhibition) was reduced in PCP-Iso, as were cognitive effects of a 5-HT6 antagonist in a hippocampal glutamate-dependent novel object discrimination task. Yet mGlu7 antagonist-evoked glutamatergic and cognitive responses were spared. Immunohistochemical analyses suggest these findings (which mirror the apparent lack of clinical response to 5-HT6 antagonists in schizophrenia) are not due to reduced hippocampal 5-HT input in PCP-Iso, but may be explained by reduced calbindin expression. This calcium-binding protein is present in a subset of GABAergic interneurons receiving preferential 5-HT innervation and expressing 5-HT6 receptors. Its loss (in schizophrenia and PCP-Iso) would be expected to reduce interneuron firing and potentially prevent further 5-HT6 antagonist-mediated disinhibition, without impacting on responses of VIP-expressing interneurons to mGlu7 antagonism. This research highlights the importance of improved understanding for selection of appropriate preclinical models, especially where disease neurobiology impacts on cells mediating the effects of potential therapeutics

Moth biomass increases and decreases over 50 years in Britain

Steep insect biomass declines ('insectageddon') have been widely reported, despite a lack of continuously collected biomass data from replicated long-term monitoring sites. Such severe declines are not supported by the world’s longest running insect population database: annual moth biomass estimates from British fixed monitoring sites revealed increasing biomass between 1967 and 1982, followed by gradual decline from 1982 to 2017, with a 2.2-fold net gain in mean biomass between the first (1967–1976) and last decades (2008–2017) of monitoring. High between-year variability and multi-year periodicity in biomass emphasize the need for long-term data to detect trends and identify their causes robustly