Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo

Plant-derived cannabinoids (phytocannabinoids) are compounds with emerging therapeutic potential. Early studies suggested that cannabidiol (CBD) has anticonvulsant properties in animal models and reduced seizure frequency in limited human trials. Here, we examine the anti-epileptiform and anti-seizure potential of CBD using in vitro electrophysiology and an in vivo animal seizure model, respectively. CBD (0.01-100 muM) effects were assessed in vitro using the Mg(2+)-free and 4-aminopyridine (4-AP) models of status epilepticus-like epileptiform activity in hippocampal brain slices via multi-electrode array (MEA) recordings. In the Mg(2+)-free model, CBD decreased epileptiform local field potential (LFP) burst amplitude (in CA1 and dentate gyrus (DG) regions) and burst duration (in all regions) and increased burst frequency (in all regions). In the 4-AP model, CBD decreased LFP burst amplitude (in CA1, only at 100 muM CBD), burst duration (in CA3 and DG), and burst frequency (in all regions). CBD (1, 10 and 100 mg/kg) effects were also examined in vivo using the pentylenetetrazole (PTZ) model of generalised seizures. CBD (100 mg/kg) exerted clear anticonvulsant effects with significant decreases in incidence of severe seizures and mortality in comparison to vehicle-treated animals. Finally, CBD acted with only low affinity at cannabinoid CB(1) receptors and displayed no agonist activity in [(35)S]GTPgammaS assays in cortical membranes. These findings suggest that CBD acts to inhibit epileptiform activity in vitro and seizure severity in vivo. Thus, we demonstrate the potential of CBD as a novel anti-epileptic drug (AED) in the unmet clinical need associated with generalised seizures.

A cost-effective high-throughput digital system for observation and acquisition of animal behavioral data

We have designed and implemented a low-cost digital system using closed-circuit television cameras coupled to a digital acquisition system for the recording of in vivo behavioral data in rodents and for allowing observation and recording of more than 10 animals simultaneously at a reduced cost, as compared with commercially available solutions. This system has been validated using two experimental rodent models: one involving chemically induced seizures and one assessing appetite and feeding. We present observational results showing comparable or improved levels of accuracy and observer consistency between this new system and traditional methods in these experimental models, discuss advantages of the presented system over conventional analog systems and commercially available digital systems, and propose possible extensions to the system and applications to nonrodent studies.

Development of multi-electrode array screening for anticonvulsants in acute rat brain slices

The acute hippocampal brain slice preparation is an important in vitro screening tool for potential anticonvulsants. Application of 4-aminopyridine (4-AP) or removal of external Mg2+ ions induces epileptiform bursting in slices which is analogous to electrical brain activity seen in status epilepticus states. We have developed these epileptiform models for use with multi-electrode arrays (MEAs), allowing recording across the hippocampal slice surface from 59 points. We present validation of this novel approach and analyses using two anticonvulsants, felbamate and phenobarbital, the effects of which have already been assessed in these models using conventional extracellular recordings. In addition to assessing drug effects on commonly described parameters (duration, amplitude and frequency), we describe novel methods using the MEA to assess burst propagation speeds and the underlying frequencies that contribute to the epileptiform activity seen. Contour plots are also used as a method of illustrating burst activity. Finally, we describe hitherto unreported properties of epileptiform bursting induced by 100M4-AP or removal of external Mg2+ ions. Specifically, we observed decreases over time in burst amplitude and increase over time in burst frequency in the absence of additional pharmacological interventions. These MEA methods enhance the depth, quality and range of data that can be derived from the hippocampal slice preparation compared to conventional extracellular recordings. It may also uncover additional modes of action that contribute to anti-epileptiform drug effects

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes.

Interpretation of infant facial expression in the context of maternal postnatal depression

Postnatal maternal depression is associated with difficulties in maternal responsiveness. As most signals arising from the infant come from facial expressions one possible explanation for these difficulties is that mothers with postnatal depression are differentially affected by particular infant facial expressions. Thus, this study investigates the effects of postnatal depression on mothers’ perceptions of infant facial expressions. Participants (15 controls, 15 depressed and 15 anxious mothers) were asked to rate a number of infant facial expressions, ranging from very positive to very negative. Each face was shown twice, for a short and for a longer period of time in random order. Results revealed that mothers used more extreme ratings when shown the infant faces (i.e. more negative or more positive) for a longer period of time. Mothers suffering from postnatal depression were more likely to rate negative infant faces shown for a longer period more negatively than controls. The differences were specific to depression rather than an effect of general postnatal psychopathology—as no differences were observed between anxious mothers and controls. There were no other significant differences in maternal ratings of infant faces showed for short periods or for positive or neutral valence faces of either length. The findings that mothers with postnatal depression rate negative infant faces more negatively indicate that appraisal bias might underlie some of the difficulties that these mothers have in responding to their own infants signals.

Evidence-based psychological therapies: from bench to bedside

Patients with mental health difficulties do not always receive appropriate and recommended psychological treatment for their difficulties, and clinicians are not always appropriately trained to deliver them. This paper considers why this might be the case and provides an overview of the Charlie Waller Institute, a not-for-profit organisation funded by the NHS, University of Reading, and the Charlie Waller Memorial Trust. The Institute seeks to address this problem by training clinicians in wide variety of evidence-based therapies and assessing the impact of this training on clinician knowledge and skill.