Lifelong Impact of Variations in Maternal Care on Dendritic Structure and Function of Cortical Layer 2/3 Pyramidal Neurons in Rat Offspring

Maternal licking and grooming (LG) exerts profound influence on hippocampal development and function in the offspring. However, little information is available on the effects of variations in maternal care on other brain regions. Here we examined the effects of variation in the frequency of maternal LG on morphological and electrophysiological properties of layer 2/3 pyramidal neurons in the somatosensory cortex in adult offspring. Compared to low LG offspring, high LG offspring displayed decreased dendritic complexity, reduced spine density and decreased amplitude of spontaneous postsynaptic currents. These changes were accompanied by higher levels of reelin expression in offspring of high LG mothers. Taken together, these findings suggest that differential amount of naturally-occurring variations in maternal LG is associated with enduring changes in dendritic morphology and synaptic function in layer 2/3 pyramidal neurons of the somatosensory cortex

Size Matters: Comparing the MDMA content and weight of ecstasy tablets submitted to European drug checking services in 2012-2021

Purpose The 3,4-methylenedioxymetamphetamine (MDMA) content in ecstasy tablets has increased enormously throughout Europe across the past decade. This study aims to determine whether this is caused by the production of “stronger” tablets (more mg MDMA per mg of tablet), or if tablets have simply been getting larger and heavier (more mg of tablet in total). Design/methodology/approach A data set of 31,716 ecstasy tablets obtained in 2012–2021 by 10 members of the Trans European Drug Information (TEDI) network was analysed. Findings The MDMA mass fraction in ecstasy tablets has remained virtually unchanged over the past 10 years, with increased MDMA contents being attributed almost exclusively to increased tablet weight. These trends seem to be uniform across Europe, despite varying sampling and analytical techniques being used by the TEDI participants. The study also shows that while tablet weight correlates perfectly with MDMA content on a yearly basis, wide variations in the MDMA mass fraction make such relations irrelevant for determining the MDMA content of individual tablets. Research limitations/implications These results provide new opportunities for harm reduction, given that size is a tangible and apparently accurate characteristic to emphasise that one tablet does not simply equate to one dose. This is particularly useful for harm reduction services without the resources for in-house quantification of large numbers of ecstasy tablets, although the results of this study also show that chemical analysis remains crucial for accurate personalised harm reduction. Originality/value The findings are both new and pertinent, providing a novel insight into the market dynamics of ecstasy tablet production at a transnational level

Methodological advances in imaging intravital axonal transport.

Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions

Applying and implementing future-oriented methods on a national level; towards enhanced policy and service preparedness to threats in the drugs domain

Background Developments in the area of drugs are evolving rapidly and new threats request countries to step up to address these challenges. Meanwhile, most drug policies and services are still grounded in response approaches that address issues of the past decades (e.g. problematic heroin and cocaine use). The current rise of prevalence and use of synthetic opioids (SO) in a number of countries in Europe stresses the need to become better prepared in order to prevent further harm. More innovation and future-oriented strategies are needed to address other current and future developments in the drug&nbsp;field. The presentation will first describe how to identify and respond to known and currently ongoing threats. The second part will describe how foresight research can contribute to national drug information systems for better preparedness and how it can be developed and implemented at national&nbsp;levels. Methods A combination of more traditional multi-source qualitative research (literature research, Reitox workbook consultations, key stakeholder interviews and focus groups) is combined with more innovative future-oriented approaches (e.g. horizon scanning, scenario development and back-casting). Outcomes are used to actively support research agencies, policymakers and services. Multiple workshops and national dialogues will be facilitated in order to implement these methods on a national&nbsp;level. Results On preparedness of the known threat of Synthetic Opioids. Research indicates that European countries are likely to face increases in prevalence and use of SO. All countries in Europe are recommended to become well prepared in terms of monitoring and responses. In order to support that process a set of implementation guides on effectively respond to synthetic opioids substances is&nbsp;developed. On preparedness to currently ongoing threats. Through literature research and questionnaires to Reitox National Focal Points and through a European civil society network, the current situation in Europe in terms of patterns in drug use, people who use drugs, societal developments, patterns in drug markets has been summarized. On a national level, drug researchers and policy makers can use this information to respond&nbsp;accordingly. Foresight research is applied on a European and on a national level (in 6 countries) for the&nbsp; identification of possible threats in the (mid-term) future that are shaped by current societal developments. On the basis of this scanning exercise, various response national scenarios will be developed and implications will discussed by national key&nbsp;stakeholders. Conclusions and&nbsp;discussion Multi-method research, using traditional and more innovative methods, is effective in supporting better monitoring and intervention activities. It proves useful in preparing for particular possible trends&#8239;—&thinsp;like with SO&#8239;—&thinsp;and it will be useful for other similar developments in substance prevalence, trade and&nbsp;consumption. In order to supports enhanced preparedness and resilience of European countries’ drug information and intervention capacity to respond to emerging drug trends and threats, intensified research and applied implementation support is highly recommended. Targeted foresight research is a very useful instrument for national observatories, policy makers and civil society to get better insight and understanding in possible upcoming developments and respond&nbsp;accordingly. In becoming better prepared for the&nbsp;future.</p

Maternal LG affects the amplitude of spontaneous postsynaptic currents in cortical layer 2/3 pyramidal neurons.

<p>(<i>A,B</i>) Typical examples of evoked action potentials <i>(A</i>) and recordings of spontaneous postsynaptic currents <i>(B</i>) obtained from layer 2/3 pyramidal neurons in the somatosensory cortex of male adult high and low LG rats. (<i>C,D</i>) Normalized cumulative frequency (<i>C</i>) and cumulative amplitude <i>(D</i>) of spontaneous events recorded from layer 2/3 pyramidal neurons. The amplitude distribution of high LG rats is shifted leftwards as compared to low LG rats (p<0.01, Kolgomorov-Smirnov test), whereas the frequency distributions do not differ significantly.</p

Differential reelin levels in the cortex of adult high and low LG rats.

<p>(<i>A</i>) Western blots immunoprobed for reelin with three bands at 450, 370 and 180 kDA corresponding to the full length and truncated reelin fragments in high and low LG rats. (<i>B</i>) Reelin immunoreactivity expressed as a ratio in optical density for reelin/ β actin for the accumulative reelin bands from high LG and low LG rats. Data are expressed as the mean±SEM. Asterisks indicate significant differences (* p<0.05).</p

Prenatal fluoxetine exposure induces life-long serotonin 5-HT(3) receptor-dependent cortical abnormalities and anxiety-like behaviour

Selective serotonin reuptake inhibitors (SSRIs) are the first choice of drugs to treat depression and anxiety during pregnancy. However, there is evidence that in uteroexposure to SSRIs leads to adverse effects in offspring. Here we show that in mice, the adverse effects of the widely used antidepressant and SSRI fluoxetine are critically dependent on the 5-HT3receptor, the only ligand-gated ion channel in the family of serotoninreceptors. In uteroexposure to fluoxetineinducesanxiety-likebehavior in wildtype, but not in mice lacking the 5-HT3receptor. In addition to this behavioral phenotype, these mice show life-longabnormalities of cortical cytoarchitecture, which can be reversed in vitro by pharmacological block of 5-HT3receptors. Moreover, the effect of fluoxetine on the development of cortical neurons is absent in 5-HT3receptor knockout mice. These findings pinpoint the pivotal role of serotonergic signaling during development and provide a novel basis to investigate the adverse effects of the use of fluoxetine during pregnancy

Maternal LG has an effect on various components of the dendritic complexity index.

<p>To calculate the dendritic complexity index for the apical and basal dendrites of cortical layer 2/3 pyramidal neurons of high LG and low LG rats total arbor length, branch tip order, branch tip number and primary dendrite number were analyzed. Data are expressed as the mean±SEM. Asterisks indicate significant differences (* p<0.05, ** p<0.01).</p